The pharmacokinetics of ketanserin, a new serotonin S2(5HT2) antagonist, were studied in 26 patients with cirrhosis. Patients were randomised to receive either a single oral dose of ketanserin 20mg (n = 14) or 40mg (n = 8) or an intravenous dose of ketanserin 5mg (n = 4). The plasma kinetics of ketanserin and its metabolite ketanserinol were determined over 48 hours, by high pressure liquid chromatography with a fluorometric detector. Pharmacokinetic parameters were calculated using noncompartmental analysis based on a statistical moment theory. The first-pass effect of ketanserin was markedly decreased after oral administration compared with results previously obtained in healthy subjects. The peak concentration was not higher in cirrhotic patients than in controls. This result could be due to an increase in the initial volume of distribution. The production of ketanserinol was reduced in cirrhotics. A decreased mean ketanserin elimination half-life (t½= 12 ± 4 and 10 ± 3hvs16 ± 3 and 18 ± 4h in healthy controls after oral ketanserin 40mg and intravenous ketanserin 5mg, respectively) contrasted with a substantial increase in t½for ketanserinol (33 ± 13vs19 ± 4h). The volumes of distribution were also markedly reduced in patients with cirrhosis. These results suggest either a reduction in the oral dosage of ketanserin or an increase in the interval between doses in patients with cirrhosis.