Previously we reported a high ratio of free insulin-like growth factor-I (IGF-I) to total IGF-I (f/t IGF-I ratio) during early infancy when rapid growth is observed, indicating that high levels of free IGF-I (fIGF-I) may be related to the growth of infants. Rapid growth is also observed during puberty. The purpose of this study is to investigate a possible relationship between pubertal growth and fIGF-I. Here, fIGF-I and total IGF-I (tIGF-I), the f/t IGF-I ratio and proteolysis of IGFBP-3 were studied in the circulation of patients with precocious puberty and normal pubertal subjects, and they were compared with those of prepubertal and adult populations. Higher absolute plasma fIGF-I values were observed in the pubertal children (3.89+/-1.09 ng/ml, N=45) than in the normal prepubertal children (2.06+/-1.01 ng/ml, N=31; P<0.05) and adults (2.18+/-0.68 ng/ml, N=49; P<0.05). Furthermore, there was a correlation between the levels of fIGF-I and height velocity in the prepubertal and pubertal groups (r=0.722, N=76, P<0.0001). Compared to the f/t IGF-I in the prepubertal and adult populations, no increase in f/t IGF-I ratios was observed, and the proteolysis of IGFBP-3 was not detected in sera from the pubertal children. These data suggest that the increase in the absolute levels of fIGF-I is related to pubertal growth.