Forty-seven asymptomatic, healthy gay men were randomly assigned to a cognitive-behavioral stress management (CBSM) condition or an assessment-only control group 5 weeks before being notified of their HIV-1 antibody status. Seventy-two hours before and 1 week after serostatus notification, blood samples and psychometric data were collected. Control subjects showed significant increases in depression, but only slight decrements in mitogen responsivity and lymphocyte cell counts pre- to postnotification of seropositivity. Seropositive CBSM Ss did not show significant pre-post changes in depression, but did reveal significant increases in helper-inducer (CD4) and natural killer (CD56) cell counts as well as a slight increment in proliferative responses to phytohemagglutinin (PHA). Individual difference analyses suggest that the psychological buffering and immunomodulating effects of the CBSM manipulation may be attributable, in part, to relaxation skills learned and practiced or to a general willingness to comply with the intervention guidelines.