More males than females enter renal replacement therapy programs. This may reflect greater propensity of men to acquire renal disease, faster progression of renal disease, or a combination of both. In order to address this problem, autosomal dominant polycystic kidney disease (ADPKD), a well-defined genetically homogenous hereditary disorder, was studied. One hundred fifty-eight cases of the disease in adults were diagnosed by sonography and studied (73 men, 85 women); 58 of the patients had reached end-stage renal failure. Survival analysis of age at renal death revealed a significant gender difference (log-rank test, P = 0.0072): median age at renal death was 52.5 years in men and 58.0 years in women. In 64 patients with adequate sequential measurements of serum creatinine, progression of renal failure was followed retrospectively. When serum creatinine was greater than 3 mg/dL, the average rate of progression was similar in both sexes. In contrast to ADPKD, a sex difference for the age at renal death was not found in prepubertal individuals with hereditary renal diseases, ie, cystinosis or nephronophthisis. The data suggest that sex (hormones) influences evolution of renal failure.