A single administration of the inhibitor of protein synthesis cycloheximide results in the occurrence of apoptosis in rat liver. The presence of intracellular apoptotic bodies was detected as early as 2 hours after treatment. No evidence of cell necrosis could be observed by histologic and biochemical analysis. Apoptosis was followed by an increased expression of testosterone-repressed prostate message-2 RNA, a gene whose activity has been associated to apoptotic cell death in involuting rat prostate. The finding of in vivo induction of apoptosis in nonproliferating cells by an inhibitor of protein synthesis, together with the rapidity and synchrony in the occurrence of cell death make this model potentially useful for the analysis of the kinetics of the apoptotic cycle and in exploring some of the mechanisms of regulation of genes possibly involved in this type of cell death.