The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of 14C-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as 14C in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of 14C were observed in the healthy subjects whereas they were not seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the 14C was 90 hr. Although a rigorous comparison of pharmacokinetic parameters between healthy subjects and T-tube patients was not feasible due to the limited number of subjects studied, comparisons of certain trends in the pharmacokinetic profiles gave some possible insights into the role of biliary excretion and enterohepatic cycling on the disposition of isotretinoin. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of 14C-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.