This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.