Intrarenal handling of uric acid was studied in 12 patients with essential hypertension under spironolactone treatment (200 mg/day). The degree of volume depletion during treatment was assessed from the changes in body weight and plasma renin activity (PRA). The results are compared with those in patients treated with chlorthalidone (50 mg/ day). During spironolactone treatment, the serum uric acid level remained constant despite a progressive volume depletion which after 3 months reached levels identical to those achieved in the chlorthalidone-treated patients, whose serum uric acid level showed the expected rise (21%). The uric acid excretion during spironolactone treatment was markedly diminished (-28%), and thus the 24-hour clearance of uric acid was correspondingly decreased (-22%). It is concluded that spironolactone affects uric acid metabolism in two ways: it causes a decrease in uric acid renal clearance (probably mediated by the induced volume depletion and PRA elevation, as with other saluretics) and, probably, inhibits endogenous uric acid production to approximately the same degree as the clearance is decreased, so that no change in the serum uric acid level occurs. The purpose of the study was to investigate the effect of spironolactone on uric acid handling by the kidney. We found a decrease in uric acid clearance and uric acid excretion. Serum uric acid concentration did not change.