The US has charged Venezuela's President, Nicolás Maduro, and other senior officials in the country with drug trafficking crimes.
The move, which will increase tensions between the two nations, was announced by Attorney General William Barr.
The US also offered a $15m (£12.5m) reward for any information leading to Mr Maduro's arrest.
It has long accused him of leading a corrupt and brutal regime, a charge he has repeatedly rejected.
Washington backs opposition leader Juan Guaidó, who last year declared himself interim president.
The new charges represent an escalation in the longstanding US pressure campaign on Mr Maduro, which has also included sweeping sanctions on Venezuela's oil industry.
As well as Mr Maduro, the US indictment charged more than a dozen top Venezuelan officials including the country's chief justice and its defence minister.
"The Venezuelan people deserve a transparent, responsible, representative government that serves the needs of the people – and that does not…. engage in illicit narcotics trafficking," the US state department said.
"These individuals violated the public trust by facilitating shipments of narcotics from Venezuela, including control over planes that leave from a Venezuelan air base," it added.
At a news conference announcing the indictment on Thursday, Mr Barr accused Mr Maduro of working with the Colombian Farc rebel group "to flood the United States with cocaine."
"While the Venezuelan people suffer, this cabal… lines their pockets," he said.
Earlier on Thursday, Mr Maduro accused the US and Colombia of conspiring against Venezuelua and causing the violence within the country.