OBJECTIVE The aim was to investigate the receptor mechanisms for different histamine actions in proximal and distal human coronary arteries. METHODS Postmortem human coronary rings precontracted by 50 mM KCl were exposed to histamine (10(-8)-10(-4) M) in control and after treatment with 10(-5) M pyrilamine (an H1 receptor antagonist), or 10(-4) M cimetidine (an H2 receptor antagonist), and/or endothelial removal. Tension changes at the point of maximum relaxation (at 10(-5) M in most rings) were obtained. RESULTS Endothelium dependent relaxations to histamine were clearly distinguished from endothelium independent relaxations by their transient nature and their inhibition by pyrilamine, but not by cimetidine. While most distal rings (group I, n = 42/58) and only some of the proximal rings (group II, n = 10/83) showed greater than 50% relaxation with histamine, nearly half the proximal rings (group III, n = 40/83) showed only contraction. Significant differences were found between group I and III, but not II, in control [-66(SD 15.2)% v +25(20.4)%, p less than 0.001] and after pyrilamine treatment [-66(9.2)% v -25(12.0)%, p less than 0.001], cimetidine treatment [-30(25.5)% v +42(20.9)%, p less than 0.001] and endothelial removal [-24(37.1)% v +36(20.2)%, p less than 0.01]. However, a combination of cimetidine and endothelial removal resulted in a contraction to histamine which was similar among the three groups. CONCLUSIONS These results suggest that hypercontractility to histamine was found in proximal human coronary arteries, but not in distal ones, probably due to the reduction of both direct and endothelial mediated relaxations rather than to an increase in the contraction itself.