Flutamide is a nonsteroidal antiandrogen used in the treatment of prostatic carcinoma. We have investigated the disposition of flutamide and its two major metabolites in ten urological in-patients without significant liver or renal disease. After oral administration flutamide is absorbed from the gastrointestinal tract with a tmax of about 2 h. Flutamide undergoes extensive first-pass metabolism, and its major metabolites are 2-hydroxyflutamide and the hydrolysis product 3-trifluoromethyl-4-nitroaniline. After the oral administration of a single dose of 250 mg or 500 mg maximum flutamide plasma concentrations of 0.02 and 0.1 micrograms.ml-1 respectively were observed. Maximum plasma concentrations of 2-hydroxyflutamide for the same flutamide doses were 1.3 and 2.4 micrograms.ml-1 (mean of n = 2 or n = 3). Steady-state concentrations of the biologically active metabolite 2-hydroxyflutamide (0.94 +/- 0.23 micrograms.ml-1, mean +/- SD, n = 5) were found at 2-4 days after the administration of 250 mg every 8 h. The area under the plasma concentration time curve for 2-hydroxyflutamide averaged 11.4 (10.6 and 12.1) and 24.3 (21.5-29.4, n = 3) micrograms.ml-1.h for 250 mg and 500 mg flutamide orally. 2-Hydroxyflutamide and 3-trifluoromethyl-4-nitroaniline were eliminated monoexponentially with half-times of 4.3-21.9 and 4.3-17.2 h (n = 5) respectively.