To evaluate the catabolism of leucine in diabetes mellitus, the urinary excretion of beta-hydroxyisovaleric acid, a by-product of leucine catabolism, in 21 nonproteinuric type II diabetic patients with and without ketosis and 21 control subjects was measured using gas chromatography-mass spectrometry. Urinary beta-hydroxyisovaleric acid and serum leucine concentrations were higher in the 9 ketotic diabetic patients than in the 12 nonketotic diabetic patients (p less than 0.005, p less than 0.01, respectively) or in the control subjects (p less than 0.01, p less than 0.01, respectively). The serum leucine concentrations in the nonketotic diabetic patients and control subjects did not differ significantly (p greater than 0.05), but urinary beta-hydroxyisovaleric acid concentrations were significantly greater in the former (p less than 0.01). These data suggest that in type II diabetic patients the catabolism of leucine is accelerated even in the absence of ketosis and that the urinary beta-hydroxyisovaleric acid concentration is a useful marker of short-term metabolic control in these patients.