A 5-HT2-receptor antagonist (LY53857) was evaluated in the livers of male Sprague-Dawley rats receiving a dose of serotonin (5-HT) producing systemic (arterial) hypotension and low flow. The specific aim of this investigation was to determine the cross-blocking potential of a 5-HT2 blocker having low affinity for alpha-adrenergic and histamine H 1-receptors. This was a follow-up study to one which characterized the effects of normo- and hypotensive doses of 5-HT on intralobular perfusion and volumetric rates of blood flow at the inlet of periportal and outlet of centrivenous sinusoids. Twenty rats were injected intraperitoneally (i.p.) with 0.05 mg per g b.w. pentobarbital five min following an i.p. injection of 0.1 mg per 100 g b.w. LY53857. The left lobes of the livers from these rats were exteriorized and examined with intravital videomicroscopic and electro-optical methods following surgical implantation of a catheter into the ileocecal vein. This venous catheter served as the route for endoportal infusion of hypotensive dose of 5-HT (10 micrograms per 100 g b.w.) in 10 rats, while the remaining 10 rats were given an equivalent volume of its carrier as a control (0.1 ml per 100 g b.w. Ringer's solution). Injection of LY53857 completely antagonized 5-HT-elicited low flow at the inlet of periportal and outlet of centrivenous sinusoids. In addition, no change in sinusoidal internal diameter was observed following blockade of 5-HT2 receptors. These results, in the concert with those from previous studies characterizing 5-HT vasoresponsiveness in the liver, suggest that: a) constrictor 5-HT2 receptors are localized on hepatic sinusoids, and b) 5-HT-provoked hypoperfusion is mediated by activation of the 5-HT2-receptor subtype.