The aim of the present study was to investigate the prevalence of tubular dysfunction and to assess the clinical significance of low-molecular- weight proteinuria and enzymuria in children with insulin-dependent diabetes mellitus (IDDM). N,acetyl-beta-D-glucosaminidase (NAG) and beta-microglobulin (β 2M) excretion was determined in 52 children with insulin-dependent diabetes mellitus and 28 controls. Patients were grouped according to the duration of diabetes: group 1 (n = 7): less than one year; group 2 (n = 27): one to five years; groups 3 (n = 18): greater than five years. Both parameters were significantly increased in groups 2 and 3 compared to controls. Urinary β 2M levels correlated significantly with albuminuria and HbA(1C), while urinary NAG levels correlated only with HbA(1C). Two to four samples were obtained from 35 of 52 diabetic patients in the study group at one-month intervals. Of these, 23 patients had elevated NAG levels, and 22 patients increased β 2M excretion. However, only six patients displayed persistent enzymuria, and nine low-molecular-weight proteinuria. The mean (SD) of coefficients of variation of each patient was 50.45 (±28.24) for NAG and 68.25 (±42.57) for β 2M excretion. We concluded that early tubular dysfunction and/or damage occurs in IDDM but is not established in the majority of children.