Elevated lead (Pb) body burden along with high levels of environmental stress with potentially enhanced cortisol levels is a particular problem for low socioeconomic status children in the US. Since Pb and stress target the same brain regions and behavioral functions, their long-term consequences for offspring were examined here following maternal Pb and stress. Dams exposed to 150 ppm Pb in drinking water beginning 2 months prior to gestation and lactation were subjected to restraint stress 3 times per day on gestational days 16-17 yielding 4 groups: control no-stress (C-NS), control stress (C-S), Pb no-stress (Pb-NS) and Pb stress (Pb-S). Fourteen-month old male offspring of dams from the Pb-S group demonstrated significant changes in accuracy in the learning component of a repeated learning and performance (RLP). Brief exposure to cold stress (4^oC, 30 min), imposed to evaluate the stress response of offspring, did not differentiate the groups behaviorally, but the Pb-NS and Pb-S groups exhibited decreased basal corticosterone (CORT) levels and an impaired CORT response to cold stress. Catecholamine levels were determined to evaluate long-lasting effects of the combined Pb/stress exposure in mesolimbic and nigrostriatal dopamine systems. In striatum, Pb exposure alone and in combination with stress modified DOPAC levels and DA turnover; while in nucleus accumbens, DA turnover was affected by Pb alone. No major changes were obtained in frontal cortex although a decrease in NE and 5-HIAA was observed in the hypothalamus as result of Pb exposure. These results demonstrate that even prenatal Pb only can permanently modulate the stress response, a critical physiological mechanism for adaptation. ES05017 and ES01247.