In most preparations of human cord arteries perfused in vitro, infusion of 10(-7) M of serotonin leads to a biphasic pressure response starting with a transient minor vasodilatation followed by a dominant vasoconstriction. In some preparations, however, the vasoconstrictive part of the response with this dose of serotonin is less pronounced or completely absent, whereas the dilatation is stronger and more prominent. The present study deals exclusively with experiments on cord arteries displaying the latter type of serotonin reactivity, and was undertaken in order to characterize the relaxing effect of serotonin, and in particular, the role of the endothelial layer. This was accomplished by studying the response pattern before and after treatment with different drugs or removal of the endothelium. The vasodilatatory action of serotonin was found to be abolished following treatment with methysergide, significantly reduced after denudation (P <0.05), slightly reduced after exposure to methylene blue or N omega-nitro-L-arginine methyl ester (L-NAME) (non-significantly), but not affected by indomethacin. The results suggest that the relaxing effect is mediated by specific serotonin receptors and that endothelium-derived substances, possibly including nitric oxide, are involved.