Silibinin in single doses of 102, 153, 203 and 254 mg was applied as silymarin in capsules (Legalon 140) to 6 healthy male volunteers. Using a newly developed HPLC method, both diastereomers of silibinin were assayed in plasma as unconjugated compounds as well as total isomers after hydrolysis. In the dose range studied, the areas under the curves correlate linearly with the dose. On average, only 10% of total silibinin in plasma is in the unconjugated form. The ratio of the silibinin isomers is reversed, if unconjugated and total isomers are compared. For unconjugated silibinin, the half-lives are less than one hour, but the terminal half-life has probably not been observed, because already after 4-6 hours the levels fell below the limit of determination of 2.5 ng diastereomer/ml. For total silibinin, an elimination half-life of approximately 6 h is estimated. About 5% of the dose is excreted into urine as total silibinin, corresponding to a renal clearance of approximately 30 ml/min. No adverse events were noted, showing that silymarin even in high doses, up to 5 capsules of Legalon 140, is well tolerated.