OBJECTIVE To define the relationship, if any, between insulin-mediated glucose disposal and serum uric acid. METHODS Cross-sectional study of healthy volunteers. METHODS General Clinical Research Center, Stanford (Calif) University Medical Center. METHODS Thirty-six presumably healthy individuals, nondiabetic, without a history of gout. METHODS Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein-cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance. RESULTS Magnitude of insulin resistance and serum uric acid concentration were significantly related (r = .69; P less than .001), and the relationship persisted when differences in age, sex, overall obesity, and abdominal obesity were taken into account (r = .57; P less than .001). Insulin resistance was also inversely related to urinary uric acid clearance (r = -.49; P less than .002), and, in addition, urinary uric acid clearance was inversely related to serum uric acid concentration (r = -.61; P less than .001). CONCLUSIONS Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney.