In order to examine ethnic differences in pain sensitivity 51 African Americans (24 men, 27 women) and 55 individuals from Other ethnic groups (primarily Caucasian; 26 men, 29 women) were tested for pain sensitivity to ischemia, heat, and cold pressor tests after both mental stress and rest. Resting and stress-induced blood pressure (BP), plasma norepinephrine (NE), and cortisol were assessed. African Americans had lower pain tolerance relative to Caucasian/Others for all pain tests. Only the Caucasian/Other group showed the expected inverse relationship between BP and pain sensitivity. African Americans exhibited lower cortisol concentrations overall and blunted NE and systolic BP responses to stress. Only in Caucasians/Others was the relationship seen between higher stress-induced BP, cortisol, and NE levels and greater pain tolerance. The results suggest that there are alterations in endogenous pain regulatory mechanisms in African Americans, which may contribute to their greater rate of clinical pain symptoms.