To determine whether the carbohydrate content of serum proteins is related to overall glycemic control, we studied serum protein-bound hexose and glycosylated hemoglobin [HbA1(a+b+c)] in 37 ambulant diabetic patients and 32 nondiabetic controls. Protein-bound hexose was correlated with HbA1(a+b+c) in the diabetic patients (r = 0.36, P less than 0.025). The mean protein-bound hexose level of the diabetic patients was greater than that of the controls (190.8 versus 174.7 mg/dl, P less than 0.01), but diabetic patients with HbA1(a+b+c) less than 12% had a mean protein-bound hexose similar to the controls. In nine of the diabetic patients, mean protein-bound hexose and HbA1(a+b+c) were significantly reduced during a period of intensive outpatient care, while two major serum glycoproteins, haptoglobins and alpha-1-antitrypsin, were unchanged. Our findings support the hypothesis that increased glycosylation of serum proteins may occur in diabetes mellitus; this abnormality in serum protein-bound hexose may be corrected by close attention to overall glycemic control.