Normal values for the first-phase insulin release during an intravenous glucose tolerance test are not yet well defined for children and adolescents. In this study, 69 normal subjects (aged 7 to 22 years) who had no family history of type I diabetes, a normal glycohemoglobin value, and a negative islet cell antibody test result underwent a standard intravenous glucose tolerance test. The mean (+/- SEM) first-phase insulin release increased with age and pubertal status: 7 to 10 years, 93 +/- 10.1 mIU/L; 11 to 15 years, 172.7 +/- 22.3 mIU/L; and 16 to 22 years, 163 +/- 28.5 mIU/L. The mean intraindividual variability in 11 subjects who underwent a second test was 23.6%. Acute stress, as estimated by observer assessment or by blood catecholamine levels, did not significantly correlate with first-phase insulin release. We conclude that first-phase insulin release is markedly lower in prepubertal children than in adolescents and young adults.