IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene (GHRd3) on IGF1 levels was evaluated.Nine hundred and eleven healthy and 23 early pubertal girls (15 with CPP) participated and were evaluated by dual-energy X-ray absorptiometry (DXA) scans, fasting and oral glucose-stimulated insulin levels, IGF1 levels, and GHR genotyping. Fifteen girls with early puberty (13 with CPP) were treated with GNRH agonists and reevaluated after 3 and 12 months.IGF1 and insulin levels were higher in girls with CPP compared with healthy controls after adjustment for age, bone age, and breast development (all P≤0.02). IGF1 levels were only significantly positively correlated with insulin levels in girls with CPP at baseline (P≤0.03). During gonadal suppression, changes in IGF1 levels were inversely associated with changes in insulin levels (P=0.04). The GHRd3/d3 genotype was associated with significantly higher IGF1 levels (P=0.01) but not with earlier pubertal timing in healthy girls. The distribution of the GHRd3 genotypes among girls with CPP did not differ significantly from healthy girls (P=0.2).The increased IGF1 and insulin levels in girls with CPP may be causally interrelated. In addition, the GHRd3 allele positively influences IGF1 levels in a copy number-response relationship but not pubertal timing in healthy girls.