U.S. prosecutors have charged two Chinese nationals who sold fentanyl to American customers over the Internet in a massive international conspiracy case, the Justice Department announced Tuesday.

The case is unique, the department said, because the men are the first Chinese-based fentanyl manufacturers and distributors to be slapped with a label reserved for those who have control of the most prolific international drug-trafficking and money-laundering organizations.

Prosecutors identified the men charged in the case as Xiaobing Yan, 40, and Jian Zhang, 38.

Yan, the Justice Department alleged, operated websites selling fentanyl directly to U.S. customers and also ran at least two chemical plants in China that were capable of producing tons of fentanyl and fentanyl analogues. The department said that Zhang similarly ran an enterprise that made ­fentanyl in at least four labs in China and that he advertised and sold fentanyl over the Internet.

At a news conference held to announce the charges, Deputy Attorney General Rod J. Rosenstein said the cases “mark a major milestone in our battle to stop deadly fentanyl from entering the United States.” The men were labeled “consolidated priority organization targets” and are the first Chinese-based manufacturers to be given the designation.

It is unclear whether they could ever be brought to the United States to face charges. Rosenstein said that China has no extradition treaty with the United States but that U.S. authorities would share the evidence in the case with their Chinese counterparts and are “optimistic” that the Chinese would take action.

Rosenstein said he was in China two weeks ago to meet with China’s minister of public security about fentanyl and other issues.

“They are, in fact, helping us, but we need them to do more,” he said.

Federal authorities have long warned of the dangers of fentanyl, a powerful synthetic opioid that often contributes to overdoses and is sometimes added to heroin and cocaine. The substance is so dangerous, authorities have said, that it has sickened emergency responders merely handling the drug.

Rosenstein said the Centers for Disease Control and Prevention estimated that more than 20,000 Americans were killed by fentanyl and fentanyl analogues in 2016. Investigators think nearly all of it and its components originate in China, he said.

The cases against Yan and Zhang originated domestically. In Yan’s case, Rosenstein said, a 2013 traffic stop in Mississippi helped uncover a drug ring selling bath salts, and investigators working that case identified Yan as a distributor of several illegal drugs.

His illicit work, Rosenstein alleged, spanned at least six years and included monitoring legislation and law enforcement activities in the United States and China to try to evade prosecution. Fentanyl’s chemical structure, Rosenstein said, can be modified to create analogues that are inside the bounds of U.S. and Chinese law. Federal agents identified more than 100 distributors of synthetic opioids in Yan’s network, Rosenstein said.

Investigators were tipped to Zhang, he said, as they investigated the 2015 death of an 18-year-old who had overdosed on fentanyl in North Dakota. Tracing the source of the substance that killed the teenager took those working the case through Oregon, Canada and eventually to Zhang in China, Rosenstein said.

Authorities found that Zhang had shipped thousands of packages of fentanyl and other drugs to the United States since January 2013, Rosenstein said. Charges against him included conduct resulting in the deaths of four people from New Jersey, North Carolina, North Dakota and Oregon in 2014 and 2015, prosecutors said.

Prosecutors said that Zhang and Yan were charged with conspiracy to distribute drugs and related counts and that 21 people have been indicted on drug charges as part of the investigation.

If convicted, Yan would face a maximum penalty of 20 years in prison; Zhang would face life in prison, prosecutors said.