The effect of long-term testosterone administration on male reproductive function has been investigated in seven healthy young men age 20 to 27 years. Testosterone oenanthate (TOe) was administered in doses of 250 mg per week for 21 weeks. No toxic side-effects were observed. Libido, sexual potency, frequency of sexual intercourse and body hair development generally remained unaffected, but there was a reversible mean weight gain of 3.6 kg during TOe administration. Seminal fluid parameters and radioimmunoassayable serum FSH, LH, testosterone, and androstenedione levels were monitored before, during, and after TOe administration. The serum testosterone rose approximately by a factor of two, while the serum FSH and LH were rapidly suppressed after the initiation of the TOe therapy. The mean sperm concentration fell to values below three million spermatozoa per ml, and changes in sperm motility, the percentage of normal sperm morphology, and seminal fructose concentrations generally paralleled those of the mean sperm concentrations. In contrast, the mean seminal fluid volume and serum androstenedione levels did not change significantly during TOe administration. The mean sperm concentration showed a marked recovery 13 to 16 weeks after TOe withdrawal, but sperm counts remained below pre-treatment levels in three out of seven subjects 25 to 28 weeks after discontinuation of TOe.