The objectives of this study were to determine 1) whether immune changes relevant to HIV progression occurred in HIV-seropositive men after the death of their intimate partner, and 2) whether depressed mood was associated with these immune changes. The bereaved group consisted of 39 gay men whose intimate partners had died of AIDS over the past year; the nonbereaved group consisted of 39 age- and HIV serostatus-matched nonbereaved men. Immunological parameters were assayed from blood samples drawn before and within 1 year after the death of the partner (bereaved group) or over an equivalent time period (nonbereaved group). In the HIV-seropositive bereaved men only, a significant increase in immune activation and a significant decrease in the proliferative response to phytohemagglutinin occurred after the death of the partner. These immunological changes were not explained by the use of recreational drugs, alcohol, cigarettes, or AZT. These data indicate that the death of an intimate partner in HIV-positive men is associated with immune changes that are relevant to HIV progression.