The effect of cyclosporin on endothelium-dependent relaxation of human subcutaneous resistance vessels was investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Acetylcholine-induced relaxation was shown to consist of at least two components, one mediated through vasodilatory prostanoids, the other through endothelium-derived relaxing factor (EDRF). Incubation with cyclosporin inhibited endothelium-dependent relaxation, as assessed by the response to acetylcholine. The inhibitory effect of cyclosporin on the acetylcholine response was most marked in the presence of methylene blue, which is an inhibitor of EDRF. This suggests that the inhibition of endothelium-dependent relaxation by cyclosporin is mediated by an effect on vasodilatory prostanoids.