Uric acid metabolism was investigated in 27 overweight subjects, 11 men (176 +/- 30 percent of ideal body weight) and 16 women (169 +/- 20 percent of ideal body weight). They were all hospitalized and treated with low-calorie diets (1,500-800 kcal/day) with gradual reduction of total calorie intake; exercise therapy (walking, and riding a bicycle ergometer) was added to this regimen afterwards. On admission, serum levels of uric acid were significantly elevated to 9.2 +/- 1.9 mg/dl in males (control 5.1 +/- 0.8 mg/dl) (P less than 0.001) and 6.8 +/- 1.9 mg/dl in females (control 4.4 +/- 1.0 mg/dl) (P less than 0.001), while the ratios (percentages) of uric acid clearance (CuA) to creatinine clearance (Ccr) were significantly reduced to 4.0 +/- 2.1 percent in males (control 10.8 +/- 2.2 percent) (P less than 0.001) and 5.2 +/- 3.1 percent in females (control 11.8 +/- 2.9 percent) (P less than 0.001). Urinary urate excretions were also lower in obese subjects than in controls. These data suggest that hyperuricemia in obese people is mainly attributed to an impaired renal clearance of uric acid rather than overproduction. In the course of weight reduction by a low-calorie diet, CuA/Ccr ratios gradually rose up to almost normal levels and serum levels of uric acid fell without significant changes in creatinine clearance. This increase of CuA/Ccr ratio was also preserved after starting exercise therapy. The normalization of urate excretion was observed even at the phase when their body weight was not fully reduced. Although the underlying mechanism of the impaired urate excretion in obese patients and its improvement during weight reduction is as yet unclear, hyperuricemia associated with obesity can be treated very well only with appropriate diet therapy and in most cases there is no need for drug therapy.