Sons of drugs kingpin "El Chapo" are among members of Mexico's Sinaloa cartel charged in the United States with running a huge operation that supplies fentanyl to the US.
The operation was allegedly fuelled by Chinese chemical companies.
Fentanyl is responsible for the deaths of tens of thousands of mainly young Americans each year.
Joaquín "El Chapo" Guzmán, the former Sinaloa cartel leader, is serving a life sentence in the US.
His three sons charged - Ovidio Guzmán López, Jesús Alfredo Guzmán Salazar and Iván Archivaldo Guzmán Sálazar - are known as the Chapitos, or little Chapos, and are believed to be the more violent faction of the cartel.
"They know that they're poisoning and killing Americans. They just don't care because they make billions of dollars doing it," Anne Milgram, chief of the US Drug Enforcement Administration, said of Guzman's sons.
"Their greed is shocking and without bounds."
Federal prosecutors announced three separate indictments charging 28 defendants based in Mexico, China and Guatemala, eight of whom are in custody.
Attorney General Merrick Garland called it "the largest, most violent, most prolific fentanyl trafficking operation in the world".
Fentanyl is a synthetic opioid that is up to 50 times stronger than heroin and 100 times stronger than morphine, according to the United States' Centers for Disease Control and Prevention (CDC).
Ovidio Guzman Lopez, one of El Chapo's sons nicknamed "The Mouse" who was arrested in Mexico earlier this year, is the only brother in custody and awaiting extradition.