The intent of this study was to examine the effects of stress-like plasma corticosterone (CS) elevation on the generation of alloantigen-specific cytotoxic T lymphocyte (CTL) activity in mice. Elevation of plasma CS was achieved by infusion of exogenous CS via osmotic pumps. CS infusion at 16 mg/kg/day on days -4 through 10 relative to alloantigen challenge led to slight, but significant, suppression of CTL activity on day 10 but no elevation of plasma CS levels. Infusion of lower CS doses (1, 2, 4 or 8 mg/kg/day) had no effect on CTL activity. Serial sampling of mice infused with CS at 0.09, 0.9 or 9 mg/kg/day over a 14-day period indicated that only the 9 mg/kg/day infusion rate caused significant plasma CS elevation. Peak CS levels (approximately 500 ng/ml) were observed 1 day after the start of CS infusion, but CS levels fell to below 200 ng/ml by day 7 and were approximately 50 ng/ml on day 12 indicating that elevated plasma CS levels could not be maintained for extended periods by CS infusion. An attempt to define the windows of CS sensitivity during CTL development was made by infusing mice with CS at doses of 10-16 mg/kg/day on days 0-3, 3-6, 4-7, 5-8 and 6-9, relative to alloantigen challenge; however, CS infusion had no effect on CTL activity. In contrast, dexamethasone infusion (9.4 mg/kg/day) on days 0 to 3 suppressed CTL activity by approximately 90% indicating that the generation of CTL activity is sensitive to high dose GC treatment, but is refractory to stress-like CS elevation. In mixed lymphocyte-tumor cell cultures, CTL activity was suppressed by CS (2.5 x 10(-8) M) if added on the first day of culture but not if added on subsequent days. These results suggest that CTL are most sensitive to CS-induced suppression if exposed near to the time of alloantigen challenge.