The influence of gender and age on adenylyl cyclase activity was investigated, through a Dowex-alumina double step chromatographic procedure, in the prefrontal cortex, hippocampus and dorsal raphe nuclei obtained from autopsy cadavers. Results showed that forskolin-stimulated enzyme activity in raphe nuclei was greater in men than in women; a region-dependent rank order of basal, forskolin-induced adenylyl cyclase activity and percentage forskolin-stimulation was observed in women only. Lastly, basal values correlated positively with forskolin-stimulated adenylyl cyclase activity in all areas except the prefrontal cortex of the male subjects. Positive significant correlations were also found between both forskolin-stimulated enzyme activity and percentage forskolin stimulation and aging in the prefrontal cortex. Overall, the findings suggest that sex and/or age-related differences in brain adenylyl cyclase vary from one cerebral region to the other.