OBJECTIVE: Prolactin is a neurohormone that may be secreted in response to stress and also has regulatory effects on the immune system. Some, but not all, studies suggest that prolactin levels are higher than normal in persons with HIV infection. The authors measured prolactin levels in HIV-positive and HIV-negative homosexual and bisexual men to assess possible differences in levels and then examined relationships between prolactin level and measures of medical status, anxiety, depression, stress, and neuropsychological test performance. METHOD: Blood for prolactin level determination was obtained from 121 HIV- seropositive and 79 HIV-seronegative homosexual and bisexual men enrolled in a longitudinal study. The men also underwent a daylong assessment that included medical, immunological, psychiatric, psychosocial, psychosexual, and neuropsychological evaluations. RESULTS: There was no statistically significant difference in serum prolactin level among the seronegative men, the seropositive men with no or minimal physical symptoms, and the seropositive men with significant physical symptoms of HIV infection. Furthermore, within the HIV-seropositive group, the correlations between serum prolactin level and measures of depression, anxiety, stress, and neuropsychological test performance were all nonsignificant. CONCLUSIONS: Serum prolactin level does not seem to respond to HIV infection or to be related to stress or psychiatric symptoms in HIV-infected men. As none of the subjects had AIDS, the possibility cannot be ruled out that prolactin level increases in very late stages of HIV infection.