The effects of gender, aging and gender x age on the binding of the 5-HT1A receptor high-affinity agonist [3H]8-hydroxy-2(di-N-propylamino)tetralin ([3H]8-OH-DPAT), were evaluated and compared in tissues of human prefrontal, temporal, parietal, occipital cortex and hippocampus obtained from 21 autopsy subjects. The results revealed no variation with age or gender in either the [3H]8-OH-DPAT maximum binding capacity (Bmax) or dissociation constant (Kd) values. On the other hand, when separate correlations to subject ages were performed for men and women, aging effects on [3H]8-OH-DPAT Bmax and Kd were detected: in men, a significant age-dependent decrease in Kd values was observed in the occipital cortex; in women, the Bmax significantly decreased with aging in the parietal cortex and hippocampus, while increasing in occipito-cortical membranes. Overall, the present study reveals that, although neither gender nor aging 'per se' seem to modify the 5-HT1A receptor binding, gender may reveal region-specific aging effects, i.e. on receptor affinity in men and receptor density in women. Such findings should stimulate further investigation on the hypothesized existence of gender x age-related cross-connections between serotonergic system and hypothalamus-pituitary-gonadal circuits.