FedEx says it transports more than 10 million packages every day and can't police every one. Getty Images

A key test of how much responsibility shippers like FedEx Corp. and United Parcel Service Inc. bear for the contents of the packages they deliver will begin this week in federal court.

The Justice Department indicted FedEx earlier this month, charging conspiracy to distribute controlled substances because of the shipper's alleged role in transporting painkillers and other prescription drugs that had been sold illegally. FedEx is scheduled to be arraigned in the proceeding Tuesday morning in San Francisco.

UPS signed a nonprosecution agreement in March 2013 in connection with the same probe by the Drug Enforcement Agency and federal prosecutors into its dealings with prescription-drug shippers. It agreed last year to pay $40 million in a deal that required it to admit to its conduct and to start an online-pharmacy compliance program.

The crackdowns are relatively new in the shipping industry, and they mark an aggressive push by the government to combat the prescription-drug black market. They come amid the government's broader efforts to address the escalating prescription-drug problem, which has also involved targeting drug providers and pharmacies as a result of investigations over the past several years.

Beginning in 2004, federal prosecutors allege that FedEx repeatedly ignored warnings from the government that it was breaking the law by shipping drugs ordered from online pharmacies that dispensed them to those who filled out an online questionnaire.

FedEx denied any wrongdoing and said it plans to plead not guilty. "We will defend against this attack on the integrity and good name of FedEx and its employees," the company said earlier this month.

The indictment also alleges the company enacted policies to benefit from shipping prescription drugs.

In 2006, a group of FedEx sales employees asked that online pharmacies be assigned to a "catchall" classification so that lost sales wouldn't affect their sales goals and therefore compensation, according to the indictment. "I can assure you these types of accounts will always result in a loss at some point. They have a very short life span and will eventually be shut down by the DEA," a FedEx managing director stated to a FedEx vice president, according to the indictment.

A senior sales analyst said in an e-mail to sales employees that FedEx would move the accounts to that classification in 2007, describing the accounts as "here one day and gone the next," according to the indictment.

Some pharmaceutical deliveries were slated for vacant homes and parking lots, according to the indictment, which charges FedEx with 15 counts, including conspiracy to distribute controlled substances and conspiracy to distribute misbranded drugs, as well as distribution of controlled substances and misbranding drugs. If found guilty, FedEx faces a potential fine of at least $1.6 billion, along with restitution and forfeiture of profits.

"This indictment highlights the importance of holding corporations that knowingly enable illegal activity responsible for their role in aiding criminal behavior," U.S. Attorney Melinda Haag said in a statement.

For the package-delivery industry, responsibility largely boils down to whether the carrier knew it was shipping illegal material, said Larry Cote, a drug-enforcement compliance attorney at Quarles & Brady LLP.

FedEx said in its statement regarding the indictment earlier this month that it transports more than 10 million packages every day and can't police every one. In addition, it said it has repeatedly asked the government for a list of shippers engaged in illicit activities but hasn't received one. "Whenever DEA provides us a list of pharmacies engaging in illegal activity, we will turn off shipping for those companies immediately," said Patrick Fitzgerald, senior vice president of marketing and communications, in the statement.

Carriers have differing methods for trying to prevent illegal materials from being shipped.

UPS has layers of internal security, the specific details of which the company can't discuss, said spokeswoman Susan Rosenberg. "We do not open every package," she adds. "We have the right to open and inspect if we choose." UPS keeps an eye out for contraband, and it won't ship any medical marijuana, even in states where it us legalized, she added.

The company also won't transport wine or firearms unless the sender follows specific stipulations. Under no circumstances will it ship human remains, common fireworks, laboratory rats or industrial diamonds, according to Ms. Rosenberg.

FedEx said in its statement that it has collaborated with law enforcement "to help stop illegal drug activity and bring criminals to justice. These efforts include providing assistance to the DEA in combatting rogue Internet pharmacies."

The U.S. Postal Service, which delivers to about 153 million addresses nationwide, functions differently. It cannot open boxes without a federal warrant.

The Postal Service has its own law-enforcement division, the U.S. Postal Inspection Service, which enforces more than 200 federal statutes using "investigative techniques looking at various trends," according to Lori McCallister, a postal inspector.

"Our spectrum of what we are looking for and how we look for them really does run the gamut," she added, saying she can't divulge any more information about USPS security techniques to keep from jeopardizing its operations.

The department does look for counterfeit goods, including sneakers, DVDs and pharmaceuticals. Ms. McCallister said her team has found live snakes wrapped in pillowcases, as well as bones and a dead fox intended for a taxidermy shop (the box was leaking blood).

But unlike FedEx and UPS, the Postal Service isn't liable for contents in the boxes it ships; the sender is.

Senders know that, said David Herzig, a Valparaiso University law professor. "If you're going to do something bad, you don't want to send it through USPS" because the punishment will be harsher if you're caught, he said. Mr. Herzig questioned whether other carriers should be held more responsible for the contents of a box than the Postal Service.

Companies like FedEx and UPS "don't know whether the contents of the box are lawful or not lawful," said Scott Greenfield, a criminal defense lawyer who owns his own firm in New York. "Nor is it their responsibility to become super cop, to pry into the box," he added, "nor do we want them to."

Now that the government has shown a new aggressiveness in pursuing companies for criminal behavior, however, carriers need to take the right legal steps to police their own activities, said Sharon L. McCarthy, a white-collar defense attorney at Kostelanetz & Fink LLP.

"In the current environment, where lots of corporations and institutions are being criminally charged," it's important to respond and to be transparent, she said.

Write to Laura Stevens at