Exposure to stressors often alters the subsequent responsiveness of many systems. The present study tested whether prior exposure to inescapable tailshock (IS) alters the corticosterone (CORT) or adrenocorticotropin hormone (ACTH) response to either an injection of bacterial endotoxin (lipopolysaccharide; LPS) or subsequent placement on a pedestal. Rats were exposed to IS or remained as home cage controls (HCC). 1, 4, 10, or 21 days later animals were injected i.p. with either 10 microg/kg LPS or equivolume sterile saline. Prior IS significantly increased plasma CORT 1 h, but not 2 or 5 h after LPS, compared to controls 1, 4, and 10 days, but not 21 days after IS. Exposure to IS 24 h earlier also significantly increased plasma ACTH 1 h after LPS. Additional animals were placed on a pedestal 24 h after IS, and plasma CORT was measured 15, 30, and 60 min later. IS significantly increased plasma CORT 15 min after pedestal exposure, but not after 30 or 60 min. These results suggest that exposure to IS sensitizes the CORT and ACTH response to subsequent HPA activation.