Caspase-3 activity and the levels of DNA fragments of 200-600 and >4000 b.p. were estimated in the cerebellar vermis, the hippocampus, and the prefrontal cortex of the brains of adult rats four and 24 months after training to extinction of the acoustic startle reaction and conditioned fear. Differently timed changes in the levels of biochemical markers of apoptosis were seen to different extents in these brain areas after training. These changes were characterized by a decrease in caspase-3 activity in the cerebellar vermis and the hippocampus, with decreases in DNA fragmentation in the hippocampus and cerebral cortex and increases in measures of programmed cell death in the hypothalamus. These experimental data support the view that the apoptosis of cells in the mature brain is involved in the mechanisms of learning and memory.