Ritanserin is a thymosthenic agent with an extensive hepatic metabolism and long elimination half life in healthy volunteers. It has been used in abstinent chronic alcoholic patients showing an interesting performance in this condition. Ritanserin pharmacokinetics has only been evaluated in single dose healthy volunteer studies and, on the other hand, chronic use of the drug in alcoholic patients during withdrawal period could be anticipated. Therefore, the objective of the present study, is to assess the cumulating kinetics of the serotonin antagonist during chronic administration. Ten abstinent alcoholic patients were included in an open study. The drug was administered at a daily dose of 10 mg for 28 days and the active phase was preceded by a seven-day wash out period with placebo. Blood samples were taken on the 1st, and 28th, day of treatment, 24 hours after taking the drug. Urine samples were taken during the night before the second and 28th dose. Plasma and urine ritanserin concentration was measured by high performance liquid chromatography. Very large variations in initial and steady state concentrations (CV = 65 and 52% respectively) were found, which is reflected in the large variability of the calculated pharmacokinetic parameters. Ritanserin cumulation factor (R) was 6.9 +/- 8.3 (mean+SEM). Two patients showing extensive accumulation had prolonged elimination half lives (433 and 279 hours) that are explained mostly by an expansion of the volume of distribution and, to a lesser extent, by diminished clearance.