A Guatemalan judge ordered former President Jorge Serrano arrested on 15 charges, including embezzling state funds.
Serrano, who was ousted in 1993 after he tried to seize dictatorial powers, said from exile in Panama that prosecutors had no case.
Guatemala has tried three times to have Serrano extradited from Panama. But this is the first time it has issued a warrant for his arrest.
A warrant also was issued for former Interior Secretary Francisco Perdomo Sandoval.