Insulin resistance and poor growth during adolescene in IDDM have been linked with reduced IGF bioactivity and elevated GH levels. In a double blind placebo controlled study we have examined the effects of a single sc injection of rhIGF-1 (40ug/kg) on total IGF-I, IGF-BP1, IGF-BP3 and GH concentrations in 9 adolescents with IDDM (aged 14-18y, Tanner Stage 4 or 5, HbA1 range 7.1-17X). RhIGF-I or placebo were given at 18.00h, blood glucose was clasped around 5mmol/L between 02.00-008.00h to assess insulin sensitivity, and sampling was continued for a total of 22 h. Peak IGF-I levels were achieved at 5.5h and declined with a T/2 of 17.3h. Mean levels were 350±26 ng/ml after rhIGF-I vs 204±21 ng/nl on control night (p<.001). Both IGF-BP1 and IGF-BP3 tended to be higher after rhIGF-I.IGF bioactivity was increased by 56X. Overall mean GH concentrations were reduced after rhIGF-I (16.9±3.2 vs 27.7±4.6 mU/l, p<0.001) and there was no evidence of rebound GH secretion over 22h. During the stable clamp period, insulin requirements following rhIGF-I were reduced (0.25±0.12 vs 0.31±0,07 mU/kg/min, p<0.03) as were levels of free insulin (31.9 ± 2.7 vs 67.9 ± .16 mU/L, p<0.001). BOHbutyrate and acetoacetate tended to be lower during rhIGF-I administration whereas lactate levels were unchanged. RhIGF-I adninistration in adolescents with IDDM results in a significant result of increased free IGF-I or reduced GH concentrations.