OBJECTIVE Uncontrolled studies have shown that women with gout have higher serum urate concentrations and similar or lower urinary uric acid excretion rates than do men with gout. These observations suggest a more defective tubular transport of uric acid in women than in men with gout. In this prospective study we assessed purine metabolism in women with primary gout under controlled conditions. We also examined whether there are sex-related differences in plasma and urinary purine concentrations among patients with primary gout. METHODS Ten women with crystal-proved primary gout and normal serum creatinine levels (below 116 mmol/L) were studied while they were on a purine-restricted diet and taking no medications known to influence uric acid metabolism. For comparison, 20 men with primary gout and 10 women without gout, matched for age, race, and body mass index, were studied under the same conditions. In each subject, plasma and 24-hour urinary uric acid, hypoxanthine, and xanthine concentrations were measured. The mean of three consecutive determinations for plasma purines and five for urinary purines was used. Standard formulas were used to calculate the renal clearances and the fractional excretion of purines. RESULTS Mean plasma urate, hypoxanthine, and xanthine levels were significantly higher in women patients with primary gout compared with normal women (P < 0.05). Mean 24-hour urinary uric acid excretion was similar in both groups. Daily urinary hypoxanthine and xanthine excretion rates were significantly lower in gouty women patients than in control women (P < 0.05). The renal clearances and the fractional excretion of uric acid, hypoxanthine, and xanthine were markedly lower in women with primary gout than in control women (P < 0.05). Plasma and urinary purine concentrations were similarly increased and diminished, respectively, in women and men patients with primary gout. Plasma urate, hypoxanthine, and xanthine levels were inversely and significantly associated with the fractional excretion of uric acid (r = -0.520; P = 0.003), hypoxanthine (r = -0.555; P = 0.002), and xanthine (r = -0.384; P = 0.040), respectively. CONCLUSIONS Women with primary gout have markedly diminished uric acid, hypoxanthine, and xanthine excretion rates. The disturbance of purine metabolism appears to be of a similar magnitude to that observed in gouty men. The absence of significant sex-related differences in plasma and urinary purine concentrations suggests a similar tubular dysfunction for purine excretion in women and men with primary gout.