Changes in the expression of the nitric oxide synthase isoforms (NOS) have been implicated in age-related neurodegeneration, although mechanisms responsible for specific differences such as reduced cognitive and motor functions are not well understood. Immunohistochemical examination of the age-dependent NOS-I and NOS-II expression in aging rats at 3, 12, 24, 36 months of age as well as in 36 months old rats who spent their last 3 months in an enriched environment, revealed a significant decrease in NOS-I expression with aging. In contrast, NOS-II increased at 36 months. Old rats kept under enriched environmental conditions, however, showed strongly reduced NOS-II expression. These results indicate that both NOS-I and II may contribute to age-related degenerative processes, but in contrast to NOS-I the age-dependent changes of NOS-II are reduced or even reversed by stimulating environmental conditions.