Evaluation of testicular function in 13 hemodialyzed patients revealed the following: plasma testosterone (ng/100 ml) was low (less than 300 ng/100 ml) in 6 and low normal in 7 patients; sperm counts ranged from 0 to 8 million/ml and motility from 0 to 8 per cent; testicular tissue from 2 patients showed an abnormal histologic picture ranging from hypospermatogenesis to germinal cell aplasia. Follicle-stimulating hormone (FSH, ng/ml) was normal in eight (10 to 217 ng/ml), and persistently eveated in five patients (265 to 760 ng/ml). Of the latter five patients, two were azzoospermic, one had germinal cell aplasia on postmortem examination, one had virtually no viable sperms, and the other was never able to furnish ejaculate for examination. Luteinizing hormone (LH, mg/ml) was high (more than 210 ng/ml) in five and normal in eight patients. Six patients when given clomiphene showed the normal response of increased FSH and LH release. Four of the 13 patients, when restudied 6 to 12 months later and while still on dialysis, showed further deterioration of plasma testosterone and sperm counts. Four of the patients subsequently underwent successful renal transplantation. All showed improvement in sperm counts (20 to 40 million/ml, motility 40 to 90 per cent) and plasma testosterone (440 to 850 ng/100 ml). These data suggest that both germinal cell and leydig cell functions were impaired among uremic men. These dysfunctions were not correctable by hemodialysis, but were completely reversed by renal transplantation. The high FSH among patients with azzospermia indicates a responsive pituitary. The positive response to clomiphene suggests that storage as well as release of both hypothalamic and pituitary hormones were normal. Attempts to localize a single defect at the testis failed to explain the post-transplant surge of FSH which invariably proceded improvement in spermatogenesis. It is therefore postulated that a defect in that portion of the hypothalamus involved in the receipt and/or interpretation of message might be at fault in uremia.