Abnormal urinary excretion of albumin is a nonspecific sign of nephropathy, commonly occurring in persons with hypertension as well as diabetes. Transferrin, rather than albumin, is more readily excreted by the kidney in those with diabetes compared with those with hypertension alone. One hundred eighty non-insulin-dependent diabetic mellitus patients were age, race, and sex matched to 90 nondiabetic control subjects who had mild to moderate hypertension. Overnight urine collections were analyzed by immunoturbidity for albumin and transferrin. The average duration of hypertension was 11 years among controls. Mean blood pressures were 134/79 mm Hg for diabetic subjects and 145/87 mm Hg for controls (P < 0.001). Diabetic patients had higher mean excretion rates of albumin (128 micrograms/min v 49 micrograms/min; P = 0.04) and transferrin (7.3 micrograms/min v 0.9 microgram/min; P = 0.0001) and higher excretion ratios of albumin (0.179 g/g creatinine v 0.069 g/g creatinine; P = 0.02) and transferrin (0.0065 g/g creatinine v 0.0013 g/g creatinine; P < 0.001) than hypertensive controls. Ratios of transferrin to albumin excretion for those with diabetes and hypertension greatly exceeded expected ratios for those with hypertension or diabetes alone if the effects of these disorders were additive. While diabetic patients were twice as likely as controls to have abnormal albumin excretion ratios (P = 0.01), they were three times as likely to have elevated transferrin excretion ratios (P = 0.0001), even though the diabetic group was half as likely as the controls to have systolic blood pressure > or = 160 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)