The current study addressed whether physical activity can buffer stress-induced "behavioral depression" and immunosuppression. Adult, male Sprague-Dawley rats were housed with either a mobile (physically active) or immobile (sedentary) running wheel and exposed to either stress (inescapable tail shock) or no stress (home cage control). Voluntary wheel running began 4 wk before stressor exposure. Immediately before stress, all rats were administered an intraperitoneal injection of keyhole limpet hemocyanin (KLH; 200 microg), and anti-KLH Ig was measured weekly for 4 wk using ELISA. Prior physical activity reduced the stress-induced behavioral depression and prevented the stress-induced suppression of anti-KLH IgM and IgG(2a) antibodies. Anti-KLH IgG(1) was stress insensitive. These data suggest that physical activity can buffer the negative impact of stress on behavior and acquired immune function.