Effects of eperisone, an antispasmodic in skeletal muscle, were investigated in helical strips of dog saphenous artery and vein. Eperisone relaxed saphenous arteries and veins previously contracted with norepinephrine, serotonin, acetylcholine, K⁺, or Ba²⁺; but in contrast, it produced contractions in the blood vessels contracted with prostaglandin (PG) F_2α. Treatment with eperisone attenuated the contractions induced by norepinephrine and serotonin in the arteries and those by clonidine and phenylephrine in the veins. Eperisone inhibited angiotensin II-induced relaxations, mediated possibly by endogenous PGI₂, but did not alter relaxations caused by exogenous PGI₂. Treatment with eperisone (10^-5 M) potentiated the contractile response to electrical stimulation of adrenergic nerves; the potentiating effect was suppressed by yohimbine. The eperisone-induced contraction in PGF_2α-contracted arteries was inhibited by treatment with indomethacin or aspirin, although cyclooxygenase activity was not inhibited by eperisone. These results may indicate that eperisone blocks postjunctional α₁- and α₂-adrenergic, muscarinic, serotonergic receptors and prejunctional α₂ adrenoceptors and reduces PGI₂ synthesis via a mechanism other than cyclooxygenase inhibition.