Microangiopathy, one of the most important complications of diabetes mellitus in humans, is associated with increased angiogenic response and proliferative lesions in various organs. Angiogenin, a polypeptide with a molecular size of 14 kD, is a potent inducer of vascular growth. This study aimed at investigating whether serum angiogenin levels are elevated in children and adolescents (youngsters) with insulin-dependent diabetes mellitus and whether angiogenin levels are affected by duration and metabolic control of the disease. It is assumed that angiogenin levels reflect the increased angiogenesis associated with microangiopathy, whether clinically evident or not. Forty diabetic youngsters were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 y and 13.8 +/- 3.6 y, respectively). The patients' disease duration and glycosylated Hb were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. Angiogenin (ng/mL) was measured in serum samples by an enzyme immunoassay and was found to be significantly higher (mean +/- SE) in patients (353.3 +/- 20.0) than in control subjects (244.7 +/- 9.6) (p = 0.0002). Levels did not vary with age, but were significantly higher in females compared with male subjects (p = 0.01). In the diabetic youngsters no significant differences were noticed with respect to duration or metabolic control of the disease. In conclusion, serum angiogenin levels were found to be increased among diabetic youngsters, irrespective of the duration and metabolic control of the disease, as well as in female subjects, with or without diabetes.