Zinc deficiency may account for the persistence of gonadal dysfunction in a majority of uremic men despite adequate dialysis. Twenty stable patients having hemodialysis three times a week completed a double-blind trial using either 50 mg of elemental zinc as zinc acetate (10 patients) or placebo (10 patients), orally. At the end of the 6-month study period, a significant increase in the mean (+/- SE) plasma zinc (75 +/- 2 micrograms/dL to 100 +/- 2 micrograms/dL, p less than 0.001), serum testosterone (2.8 +/- 0.3 ng/dL to 5.2 +/- 0.5 ng/mL, p less than 0.001), and sperm count (30 +/- 3 million/mL to 63 +/- 5 million/mL, p less than 0.001) occurred in the zinc-treated group, but not in those receiving the placebo. The zinc-treated group also had a significant fall in serum luteinizing hormone (92 +2- 10 mIU/mL to 49 +/- 26 mIU/mL, p less than 0.005) and follicle stimulating hormone (45 +/- 9 mIU/mL to 25 +/- 7 mIU/mL, p less than 0.05), not seen in the placebo group. Patients receiving zinc had an improvement in potency, libido, and frequency of intercourse not found in the placebo group. These results suggest that zinc deficiency is a reversible cause of gonadal dysfunction in patients having regular hemodialysis.