Age-related changes in the levels of brain-derived neurotrophic factor (BDNF) in selected regions of brains from rats, normal mice and senescence-accelerated mice were compared to those of nerve growth factor (NGF) and neurotrophin-3 (NT-3). The concentration of BDNF increased with age in the rat hippocampus while it decreased in the rat cerebral cortex. The level of BDNF in the hippocampus from aged rats was about 260%, of that in the same region from young adult rats. A strong staining with antibodies specific for BDNF was observed in the hilus of the dentate gyrus in the hippocampus from aged rats. By contrast, BDNF levels were significantly lower in four brain regions from aged rats as compared to young adult rats (30, 56, 52 and 52%, lower in the septum, cerebral cortex, cerebellum and striatum, respectively). Patterns of age-related changes in the level of BDNF in the mouse hippocampus. cerebral cortex, cerebellum and olfactory bulb were similar to those in the respective regions from rats. In rats, the concentration of NGF decreased with age in the cerebral cortex but remained unchanged in the hippocampus, cerebellum and olfactory bulb. In mice, levels of NGF increased in all four brain regions from 1 to 18 months after birth. The concentrations of NT-3 increased and decreased with age in the rat cerebral cortex and cerebellum, respectively, while minimal changes were observed in the rat hippocampus and olfactory bulb as was also true in mice. In senescence-accelerated mice with memory disturbances, no marked increases in levels of NGF and BDNF in the hippocampus and in the level of NT-3 in the cerebral cortex were found. Thus, increases in levels of BDNF and NT-3 occurred in the murine hippocampus and cerebral cortex, respectively, during normal aging, but not during aging of mice with pathological changes.