The antihypertensive mode of action of the 5HT2 receptor antagonist, ketanserin (KET), is still a subject of controversy and has been evaluated predominantly in acute studies. Acute i.v. administration of KET (3.0 or 6.0 mg/kg) in spontaneously hypertensive rats resulted in dose-dependent reductions in mean arterial pressure accompanied by concomitant bradycardia. In these studies, the responses to single i.v. doses of the alpha-1 adrenoceptor agonist phenylephrine (10.0 micrograms/kg) and to the 5HT2 receptor agonist alpha-methyl-5-hydroxytryptamine (125.0 micrograms/kg) 30 min after injection of KET were blocked. In spontaneously hypertensive rats treated with KET infusions (3.0 mg/kg/day i.v., n = 9, or 6.0 mg/kg/day i.v., n = 8) for 7 days via osmotic minipumps, significant dose-dependent falls in systolic blood pressure were observed during the period of infusion. Heart rate did not change over the period of observation in both vehicle- and KET-treated groups. On day 7 of infusion, KET dose-dependently reduced responses to the 5HT2 agonist alpha-methyl-5-hydroxytryptamine (5.0-125.0 micrograms/kg i.v.) but did not affect responses to phenylephrine (1.0-10.0 micrograms/kg i.v.). Baroreflex sensitivity on day 7 was significantly greater in KET-infused rats as compared with control rats. These data confirm that the acute antihypertensive effects of KET are due to a combination of alpha-1 and 5HT2 receptor blockade. During chronic administration, however, the alpha-1 blocking effects of KET are compensated for, and the reduction in blood pressure by day 7 of KET chronic administration is maintained predominantly by persistent blockade of 5HT2 receptors.