While most distal human coronary arteries markedly relaxed in response to histamine, nearly half the proximal ones contracted only. Thus, we investigated the receptor mechanisms for those heterogeneous histamine actions. After a combination of cimetidine-treatment and endothelial removal, but neither one alone, proximal and distal rings contracted to histamine to the same degree. It is suggested that histamine hypercontractility in proximal human coronary artery is due to a lack of both direct (H2-receptor) and endothelial-mediated (H1-receptor) relaxant actions.