Inhibition of the testosterone synthesis caused by ketoconazole was studied in healthy young men. They received the drug for seven days at a dose of 200 mg daily. Neither the blood level of total plasma testosterone nor that of the free fraction showed any alteration during treatment. 24 hours after treatment, however, the response of plasma testosterone to hCG was diminished. These findings indicate a delayed effect of ketoconazole on the synthesis of testosterone, although its blood levels are decreased to nearly zero. The effects of ketoconazole are due to its binding to enzymatic proteins. Thus the link to other proteins binding androgens might be possible. Our experiments demonstrated that ketoconazole may inhibit the binding of testosterone to antibodies in a RIA system as well that to SHBG.