Because previous studies have suggested that activation of baroreceptors could mediate stress-induced analgesia, the effect of acute exposure to footshock on mean arterial pressure (MAP) and pain sensitivity was simultaneously determined in conscious rats receiving the histamine H2 receptor antagonist cimetidine or vehicle. Continuous exposure to 3 min of inescapable footshock (3.5 mA) dramatically decreased pain sensitivity, with no increase in post-stress MAP, when compared to no shock controls. The histamine H2-antagonist cimetidine (100 mg/kg, IP) had no significant effect on MAP in resting or stressed animals, but inhibited the stress-induced analgesia, showing that the antagonism of the analgesia is not mediated by modulation of post-stress MAP. Although footshock failed to elicit a significant increase in MAP, a highly significant correlation was found between individual analgesic scores and shock-induced pressure changes in animals treated with cimetidine; in animals receiving vehicle, no such correlation was observed, although the use of a cutoff in analgesic testing may explain this. These results suggest the existence of a stress-induced analgesic mechanism resistant to cimetidine, but associated with elevated MAP.