The transcapillary escape rate, intravascular mass and outflux of albumin were measured in 75 Type 1 (insulin-dependent) diabetic patients. The groups were defined as: group 1: normal urinary albumin excretion, less than 30 mg/24 h (n = 21); group 2: microalbuminuria, 30-300 mg/24 h (n = 36); group 3: diabetic nephropathy, less than 300 mg/24 h (n = 18). Fifteen sex- and age-matched non-diabetic persons served as control subjects. The diabetes duration was: group 1: 20 +/- 9 years, group 2: 17 +/- 5 years, group 3: 19 +/- 7 years. The transcapillary escape rate of albumin was similar in controls and group 1 (5.0 +/- 1.8 versus 5.2 +/- 1.5%) and was significantly higher in the microalbuminuric group 2 and group 3 (8.1 +/- 2.2 versus 8.1 +/- 2.3%). The differences were not explained by differences in metabolic control or blood pressure at the time of investigation. The outflux of albumin was also higher in group 2 than in group 1 and controls (7.1 +/- 2.0 versus 5.3 +/- 1.5 and 5.1 +/- 2.0 g/h X 1.73 m2). It was indistinguishable from controls in group 3 (5.8 +/- 1.5 g/h X 1.73 m2) because of a reduced intravascular mass of albumin (p less than 0.01) in group 3. In conclusion, a universal vascular leakage of albumin is an early event in the development of diabetic nephropathy, with the leakage of albumin being fully developed in the microalbuminuric patient. In contrast, long-term diabetic patients with normal urinary albumin excretion have a normal transcapillary escape rate of albumin.