Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 < 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater-than-or-equal-to 25 pg/ml, (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p < 0.01), but the durations since onset (> 0.5 and < 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p < 0.001) and correlated with E2 (r = 0.41, p < 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p < 0.01) and correlated with E2 (r = 0.52, p < 0.01). They were in the prepubertal range in 88% of cases in group I and in 35% of cases in group II. The mean bone age advance was slightly but not significantly lower in group I (1.8 +/- 0.3 years) than in group II (2.1 +/- 0.2 years). We concluded that the correlation between E2 and peak LH/FSH ratios indicates variable degrees of hypothalamopituitary-ovarian activation and that low E2 stimulates growth in spite of prepubertal IGF-I values, suggesting a direct effect of E2 on skeletal growth.