The action of nicorandil on vascular smooth muscles has been studied in vitro using the microelectrode, Ca-transient, isometric tension recording methods, and the bioassay methods of cyclic nucleotides and inositol phospholipids. Nicorandil increased Ca-insensitive K conductance and hyperpolarized the membrane and thus prevented the activation of the voltage-dependent Ca channel. The hyperpolarization occurred to a greater extent in venous tissue than in arterial tissue. Nicorandil stimulated the synthesis of cyclic guanosine monophosphate (cGMP) in the polarized and depolarized muscle tissues, as did nitroglycerin. Consequently, nicorandil reduces the concentrations of free Ca in the myoplasm, due to acceleration of the Ca pump at the sarcolemma, and may prevent the phosphorylation of myosin through phosphorylation of myosin light chain kinase. These actions of nicorandil may not contribute to the synthesis of inositol-1,4,5-trisphosphate hydrolyzed from phosphatidylinositol-4,5-bisphosphate. The above actions of nicorandil--hyperpolarization and increase in the cyclic GMP--may cause relaxation of the tissues precontracted by various stimulants.