The head of a Guatemalan prison and 21 employees have been arrested over the killing at the jail on Sunday of four police officers detained there.
The four policemen were arrested last Thursday
President Oscar Berger says he believes organised criminal gangs were behind the deaths in the Boqueron prison.
The authorities are trying to determine how the gunmen got past eight locked doors to shoot the four officers.
The policemen were being held in connection with last week's killing of three visiting Salvadorean politicians.
Key evidence about those assassinations would be lost with the deaths of the policemen, Mr Berger said.
The three were from El Salvador's ruling Arena Party.
Early versions had suggested their killing was politically motivated because one of them, Eduardo D'Aubuisson, was the son of Roberto D'Aubuisson, accused of running right-wing death squads in the 1980s.
Announcing the arrests of prison staff, Guatemala's prosecutor general said the 22 had claimed not to have heard any shots.
"It is incredible that being there they did not hear anything," Juan Villalta said.
"This leads us to believe that some may have been accessory to the crime and others may be the authors."
The killing of the four police officers in the maximum-security Boqueron jail 70km (43 miles) from Guatemala City, sparked a 12-hour riot among inmates.
It ended only after the prisoners - mostly members of street gangs - were allowed to tell a TV crew that they had not been behind the killings of the police officers.
One of those killed was the head of the country's organised crime unit, Luis Arturo Herrera, and three of his colleagues.
Mr Berger said it remained unclear if the deaths of the policemen were linked to drug trafficking or other organised crime.
Some reports suggest the policemen may have been murdered to stop them disclosing who ordered them to kill the Salvadoreans
The US authorities estimate that much of the cocaine entering the US comes via Guatemala.
US President George W Bush is due to travel to Guatemala in March and it is expected that the growing drugs trade will be high on the agenda.