Persistent clinical proteinuria (i.e., urinary protein excretion >0.5 g/24 h) is an ominous development in a person with diabetes. It eventually leads to a decline in the glomerular filtration rate and ultimately to end-stage renal failure or premature cardiovascular mortality. Progression of renal disease appears to be related to arterial blood pressure and protein intake and is primarily independent of the metabolic state. More s nsitive immunoassays for detecting low concentration of albumin in urine have led to recognition of subclinic l increases in albumin excretion rates in nonclinically proteinuric diabetic patients, a phenomenon named microalbuminuria. Studies have shown that patients with microalbuminuria have a significantly increased risk for clinical proteinuria and cardiovascular mortality. Microalbuminuria is rarely found during the first 5 yr of a patient's diabetes, suggesting that it is a sign of early glomerular damage rather than a marker for susceptibility to it. In patients with non-insulin-dependent diabetes mellitus (NIDDM), an association has been found between microalbuminuria and coronary heart disease, but this relationship needs further investigation. In pat ents with insulin-dependent diabetes mellitus (IDDM), this subclinical form of proteinuria is associated with poor metabolic control and, more important, with marginal elevation of blood pressure. Correction of hypergly emia by intensified insulin treatment might arrest progression to persistent clinical proteinuria; moreover, restricted protein intake and lowering of blood pressure have been shown to reduce the albumin excretion rate. Recent evidence suggests that the development of nephropathy in IDDM may be linked to a familial, possibly genetically determined, predisposition to hypertension. The identification of genetic components would enable cl nicians to focus therapy on patients at risk for development of diabetic nephropathy.