Hemolysin produced by Vibrio vulnificus caused hypotension and tachycardia in rats and dilated rat thoracic aorta. Hemolysin-induced vasodilatation of the aorta was not affected by N omega-nitro-L-arginine methyl ester and aminoguanidine, NO synthase inhibitors, whereas the vasodilatation was inhibited by LY 83,583, a guanylate cyclase inhibitor. Hemolysin elevated cGMP levels, and the elevation was abolished by LY 83,583. These results suggest that V. vulnificus hemolysin activates guanylate cyclase independently of NO synthase, and the subsequent increase in cGMP levels results in vasodilatation.