The mechanism of vasodilation effect of GS-389, 1-(4'-methoxybenzyl)-6,7 -dimethoxy-1,2,3,4-tetrhydroisoquinoline hydrocholoride, a possible cyclic GMP specific phosphodiesterase inhibitor, on rat and mouse thoracic aorta ring has been investigated. GS-389 relaxed rat and mouse thoracic aorta precontracted with phenylephrine and high K⁺(60mM) in concentration dependent manner. Presence or absence of endothelium did not alter the relaxing effects of it. GS-389 inhibited Ca²⁺-induced contraction of the high K⁺ or 1 uM phenylephrine. Initial phasic contraction induced by phenylephrine and caffeine in Ca²⁺ free solution was inhibited by GS-389. Methylene blue pretreatment suppressed relaxation effect of GS-389. Relaxation by isoproterenol or sodium nitroprusside and by acetylcholine in endotheilium preserved aorta was potentiated by concurrentadministration of GS-389. GS-389 inhibited phenylephrine-induced phosphatidylinositide hydrolysis. It is suggested that inhibition of phosphoinositide turnover associated with elevated cyclic nucleotide by GS-389 may be the possible vascular relaxation mechanism of it.