The present study demonstrates the relationship between urinary albumin excretion rate (AER) and renal structural changes in patients with non-insulin-dependent diabetes mellitus (NIDDM) without clinical proteinuria. Resting AER in 30 control subjects and 67 NIDDM patients were 10.4 ± 4.8 (mean ± SD) μg/min (range 4.3–21.1 μg/min) and 26.4 ± 32.3 μg/min (range 0.4–155 μg/min), respectively. Persistent normoall-buminuria (<20 μg/min) and microalbuminuria (20–200 μg/min) were found in 43 (Group A) and 24 (Group B) diabetics. There were significant differences in age, diabetes duration, and frequency of retinopathy (background and proliferative) as well as that of proliferative retinopathy between Groups A and B, but not in the other clinical parameters such as body mass index, HbA 1, Ccr, or systolic and diastotic blood pressure (SBP, DBP). When compared with 11 normoalbuminuric patients of similar age and equal diabetes duration to those in Group B, the sole difference in clinical parameters was the existence of proliferative retinopathy in Group B. Renal structural changes were investigated by light microscopy in 14 people in Group A and 13 people in Group B, and additionally in 5 NIDDM patients with both macroalbuminuria (≥200 μg/min) and normal or nearly normal renal function (Group C). The diffuse glomerular lesion (Gellman's classification) was grade I or II in A, II or III in B, and III in C. The nodular lesion was grade 0 in all of A, 0 or I in B, and 0, I or II in C. Arteriolar hyalinosis (Takazakura's criteria) was grade 0 or I (III in only one case) in A, II or III in B and C. Maximum AER after exercise using an ergometer varied from 2.6 to 260.4 μg/min in 16 patients in Group A. According to maximum AER induced by exercise, these patients were further classified into Groups A1 (<20 μg/min), A2 (20–100 μg/min) and A3 (≥100 μg/min). No significant differences among groups could be detected in age, diabetes duration, HbA 1, Ccr, maximum systolic blood pressure (max SBP) during exercise, frequency of retinopathy, or renal morphologic changes. The authors conclude that 1) persistent microalbuminuria in NIDDM is usually accompanied by retinopathy and rather advanced diabetic renal lesions and is predictive of future macroalbuminuria, and 2) there is no convincing clinical or renal histologic evidence indicating that greater elevations in AER after exercise are related to a higher risk for progression from normoalbuminuria to microalbuminuria