This study examined the effects of a 10-week cognitive-behavioral stress management (CBSM) intervention on dehydroepiandrosterone sulfate (DHEA-S) levels and the ratio of cortisol to DHEA-S (cortisol/DHEA-S), potential surrogate adrenal markers of HIV disease progression, in relation to alterations in mood and distress. HIV-seropositive men were randomized to either a group-based CBSM intervention (n = 43) or to a wait-list control group (n = 24), with both hormonal and distress measures assessed just prior to and immediately following the 10-week period. Results showed that CBSM buffers decreases in DHEA-S and increases in the cortisol/DHEA-S ratio. Further examination also revealed that changes in the cortisol/DHEA-S ratio were significantly and positively related to changes in total mood disturbance and perceived stress over time. These findings demonstrate that a short-term CBSM intervention can buffer against decrements in DHEA-S and increments in the cortisol/DHEA-S ratio among symptomatic, HIV-positive men, and that alterations in the cortisol/DHEA-S ratio move in concert with changes in mood and distress observed during CBSM.