The effect of warfarin administration on plasma uric acid was investigated. A representative sample of patients on long-term warfarin treatment had a significantly higher concentration of uric acid in plasma than did age-matched patients with comparable plasma urea concentrations who were not taking warfarin. In women, this association was observed only in patients with normal values for plasma urea, not in those with high values. In contrast, in men this association was present in both groups (normal and high plasma urea). In a longitudinal study involving patients, their plasma uric acid significantly increased after warfarin administration. There was no significant change in the renal clearance of uric acid after a single dose of warfarin in normal, healthy volunteers; this contrasts with the increase observed with other coumarin anticoagulants. Our findings suggest that the increase in plasma uric acid noted with warfarin administration is probably due to an increase in uric acid production and may predispose to gout those patients who are on long-term therapy with warfarin.