Current interest in the presumed benefits of wine in protecting against coronary heart disease prompted us to investigate possible effects of various grape products on vascular function in vitro. Certain wines, grape juices, and grape skin extracts relaxed precontracted smooth muscle of intact rat aortic rings but had no effect on aortas in which the endothelium had been removed. Quercitin and tannic acid, compounds known to be present in grape skins, also produced endothelium-dependent relaxation; two other grape skin compounds, resveratrol and malvidin, did not relax the rings. Phenylephrine-induced contractions were attenuated by prior exposure of aortic rings to grape skin extracts. The extracts also increased guanosine 3',5'-cyclic monophosphate (cGMP) levels in intact vascular tissue, and both relaxation and the increase in cGMP were reversed by NG-monomethyl-L-arginine and NG-nitro-L-arginine, competitive inhibitors of the synthesis of the endothelium-derived relaxing factor, nitric oxide (NO). The vasorelaxation induced by grape products therefore appears to be mediated by the NO-cGMP pathway. If such responses occur in vivo, they could conceivably help to maintain a patent coronary artery and thereby possibly contribute to a reduced incidence of coronary heart disease.