The predictive value of tubular proteinuria and/or enzyme excretion for the development of microalbuminuria in patients with diabetes mellitus was investigated over a period of 7.5 years in 64 children and adolescents without microalbuminuria at baseline. An abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) preceded the increase of albumin excretion in all 8 patients (12.5%) developing microalbuminuria during this period (positive/negative predictive value 0.2 and 1.0, respectively). Also both, the actual as well as the long-term glycemic control (HbAlc) up to the onset of abnormal NAG excretion were predictive for the development of microalbuminuria. Fifty percent of those patients with both an elevated NAG excretion and an HbAlc > or = 9% developed micro-albuminuria within the next 5 years. Therefore, periodic monitoring of urinary NAG excretion should be incorporated into the follow-up of patients with type 1 diabetes mellitus.