Testicular and plasma testosterone (T) and plasma LH levels were determined in 6 normal men. Two of these men received 50 mg testosterone propionate (TP) daily for 10 and 25 weeks, respectively. Testicular and plasma T and plasma LH assays were again performed during TP administration. The mean T concentration for 5 control testicular biopsies was 553 ng/g ± 90 sd, which was approximately 100 times higher than average normal plasma T concentrations (assuming 1 ml plasma ≅ 1 g tissue). Administration of TP resulted in the following: 1) LH was rapidly reduced to undetectable levels; 2) testicular T decreased by about 95%; 3) plasma T increased nearly 2-fold; and 4) sperm concentration dropped sharply. Since a high concentration of testicular T is known to be required for normal spermatogenesis, we conclude that the cause of the depression of spermatogenesis in men given TP is the striking reduction in testicular T.