Isolated human arterial segments have been used to demonstrate the presence and release of the endothelium derived relaxing factor (EDRF) in human vasculature. This has been shown in peripheral, splanchnic and coronary arteries. Agents which have been shown to promote the release of the human EDRF in these studies include acetylcholine (by a muscarinic mechanism), the calcium ionophore A23187, histamine and vasoactive intestinal peptide (VIP). Nordihydroguaretic acid (NDGA), methylene blue and haemoglobin reverse the effect of the EDRF. The EDRF effect is calcium-dependent and is not inhibited by indomethacin. Atheromatous disease in coronary arteries impairs the response to agents which release EDRF; its relative absence in this circumstance may play a role in the phenomenon of coronary artery spasm. The possibility of a specific alpha 2-adrenoceptor mechanism for the release of EDRF was investigated. This does not appear to be present in the human vasculature.