At least 13 prisoners died of drug overdoses after inmates stormed a prison infirmary during protests demanding better living conditions,Venezuela's government said.
But activists questioned the official version and said the death toll could be far higher.
The disturbances at the David Viloria penitentiary began on Monday when a group of inmates went on a hunger strike seeking to force out the jail's new warden, the prisons ministry said.
National Guardsmen were called in to restore calm and dozens of prisoners were transferred. The government said 145 inmates were being treated for intoxication.
The situation remains tense, and prisoner rights activists expressed doubt about the government's version, calling for an investigation to discover why inmates would have voluntarily taken highly toxic medicines.
"I don't think anyone is so stupid to ingest drugs just as a form of protest," Humberto Prado, co-ordinator of the Venezuelan Observatory of Prisons, said.
He said the death toll might be as high as 25, according to reports from inmates' relatives and activists on the ground at hospitals and the morgue in the western city of Barquisimeto, where the prison is.
The government said the situation was under control and all prisoners' rights were being respected.
Venezuela's prison population has doubled since 2008 as a result of rampant crime and stiffer mandatory sentences.
Overall, the country's 32 correction facilities are the fifth most-crowded in the world, housing almost three times their intended capacity, according to the London-based International Centre for Prison Studies.
The David Viloria prison is named for a guard who was one of 58 people killed at the facility last year during the second-deadliest prison riot in Venezuela's history.
Mr Prado said the facility, previously called La Uribana, was built to hold no more than 850 inmates but was believed to be holding around 3,700 before the latest disturbances.
His group said that so far this year 150 inmates have died and 110 more injured in the country's jails.
"Prison life is real tough in the world, but unfortunately in Venezuela it can be a death sentence," he said.