A B S T R A C T The role of follicle-stimulating hormone (FSH) in the control of spermatogenesis is not well established in any species, including man. We studied the effect of an experimentally-induced, selective FSH deficiency on sperm production in normal men. After a 3-mo control period, five normal men received testosterone enanthate (T) 200 mg i. m. weekly to suppress luteinizing hormone (LH) and FSH, until three successive sperm counts revealed azoospermia or severe oligospermia (sperm counts <3 million/ml). Then, while continuing T, human chorionic gonadotropin (hCG) 5,000 IU i. m. three times weekly was administered simultaneously to replace LH activity, leaving FSH activity suppressed. The effect of the selective FSH deficiency produced by hCG plus T administration on sperm production was determined.Sperm counts (performed twice monthly throughout the study) were markedly suppressed during T administration alone (1.0+1.0 million/ml mean± SE, compared with 106±28 million/ml during the control period, P < 0.001). With the addition of hCG to T, sperm counts returned toward normal (46±16 million/ ml, P < 0.001 compared with T alone). In two subjects, sperm counts during hCG plus T returned into the individual's control range. Sperm motility and morphology were consistently normal in all men during hCG plus T. Serum FSH levels by RIA were normal (110±10 ng/ml) in the control period and were suppressed to undetectable levels (<25 ng/ml) in the T alone and hCG plus T periods. markedly suppressed in the T alone (60±15 mIU/h2nd IRP, P < 0.01) and hCG plus T (37±9 mIU/h, P < 0.01) periods compared with the control period (334±78 mIU/h).We conclude that spermatogenesis as assessed by sperm counts, motilities, and morphologies may be reinitiated and maintained at normal levels in men with undetectable blood FSH levels and urinary excretion of FSH less than that of prepubertal children. This conclusion implies that, although FSH may exert effects on human testicular function, maintenance of normal spermatogenesis and reinitiation of sperm production after short-term suppression by exogenous steroids can occur in spite of nearly absent FSH stimulation.