To evaluate the frequency of autoantibodies to glutamic acid decarboxylase (GAD), protein tyrosine phosphatase-like protein (IA-2), and insulin (IAA) in children with type 2 diabetes mellitus (DM), we studied 37 children and adolescents whose type 2 DM was defined by fasting and 90-min standard liquid meal-stimulated serum C-peptide levels of >0.2 and >0.5 nmol/l (0.7 and 1.5 ng/ml), respectively. Mean fasting-stimulated serum C-peptide levels were 1.1 +/- 0.10 nmol/l (3.38 +/- 0.29 ng/ml) and 1.9 +/- 0.17 nmol/l (5.79 +/- 0.50 ng/ml), respectively. Eleven out of 37 patients (29.7%) were positive for at least one autoantibody: 8.1% (n = 3) had positive GAD, 8.1% (n = 3) had positive IA-2, and 27% (n = 10) had positive IAA. Nine of the 10 IAA-positive patients were on insulin treatment at the time of testing. Three of the 10 IAA-positive patients were also positive for GAD or IA-2. Since insulin treatment can stimulate IAA, we considered this to be less informative in classifying autoimmunity in DM. Therefore, GAD and IA-2 were considered primary autoimmune markers. Four out of 37 patients (10.8%) were positive for GAD (n = 3) or IA-2 (n = 3) or both (n = 2). Thus, low (10.8%) frequency of autoimmunity in children and adolescents is consistent with their clinical classification of type 2 DM based on the presence of residual C-peptide.