The serum urate concentration of adult women, which is lower than in men of a similar age, is thought to be related to a higher renal clearance of urate in women, possibly due to their higher plasma estrogen levels. Intersexual differences in the renal handling of uric acid was assessed in 9 normal adult women and 9 normal age-matched men. Women showed a significantly lower serum urate concentration as compared to men (3.5 ± 0.3 v 4.9 ± 0.7 mg/dL, P < 0.001), higher fractional excretion of urate (9.8 ± 1.0 v 7.3 ± 0.8%, P < 0.001), and significantly lower tubular urate postsecretory reabsorption (67.2 ± 1.6 v 76.6 ± 1.4% of secreted urate, P < 0.01). To test whether plasma E 2 has a uricosuric effect we administered estradiol valerate and estradiol benzoate to either oophorectomized or adult women. Plasma E 2 levels and urinary total estrogen excretion increased significantly in both groups but the treatment failed to significantly modify serum urate or the fractional excretion of uric acid. Furthermore, in 4 normal adult women, the tubular phases that modulate the renal excretion of urate were not significantly influenced by increased plasma E 2 levels. We conclude that in comparison to men of a similar age, the lower tubular urate postsecretory reabsorption of adult women is in accordance with the intersexual differences in uric acid metabolism. Plasma E 2 does not influence renal handling of uric acid or serum urate levels.