We measured concentrations of transferrin (TRF, in micrograms), and creatinine (Cr, in millimoles) in samples of untimed urine from 53 healthy subjects and 157 non-insulin-dependent diabetic (NIDD) subjects. The urinary TRF/Cr ratio was significantly higher in the NIDD group (P less than 0.001). If NIDD subjects are grouped according to their Alb/Cr ratio into normal albuminuria (Group A, Alb/Cr less than 2.5 mg/mmol), microalbuminuria (Group B, Alb/Cr 2.5-26.8 mg/mmol), and macroalbuminuria (Group C, Alb/Cr greater than 26.8 mg/mmol), the TRF/Cr ratios in all three groups exceeded those for healthy controls. Moreover, this ratio was higher in Group B than in Group A and higher in Group C than in Group B. The value for TRF/Cr was clearly abnormal (i.e., exceeded the 95th percentile value found in healthy subjects) in 61%, 95%, and 100% of Group A, B, and C subjects, respectively. The TRF/Cr ratio was significantly higher in those NIDD subjects with clinical retinopathy, and it correlated with arterial pressure. Evidently, TRF/Cr may be increased early in NIDD subjects, and it may be a sensitive marker for detecting development of complications of diabetes.