Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.