Twenty-eight elderly inpatients with severe hyponatremia were investigated prospectively to determine if fractional uric acid clearance was increased significantly in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) compared with other causes of hyponatremia. The patients were divided into three groups: Group A--hyponatremia due to SIADH, Group B--hyponatremia due to diuretic use, and Group C--hyponatremia possibly due to a number of causes. Serum uric acid was 3.2 +/- 0.4 and 5.3 +/- 0.6 in Groups A and B, respectively (P less than 0.05). Fractional clearance of urate in Groups A and B were 43 +/- 5.1 and 16.7 +/- 1.9, respectively (P less than 0.001). In Group C six of the nine had abnormally increased fractional clearance of uric acid (31.6 +/- 3.8) in addition to accepted biochemical criteria of SIADH. In 10 patients with SIADH, urate clearance measured before water restriction was 40.2 +/- 9.0%, and after serum sodium returned to normal 11.6 +/- 1.5 (P = 0.05). Of the total 28 patients 17 had increased fractional uric acid clearance with biochemical criteria of SIADH, suggesting that this syndrome is a common cause of the increased susceptibility to hyponatremia among older patients.