Little is known about the factors affecting preantral follicle growth but we have recently shown that IGF-I stimulates growth of follicles in human cortical tissue in culture (Stubbs et al, Endocrine Abstracts 2003, 6, OC7). The aim of this study was to extend the study of the effects of IGF-I on follicle recruitment and test the specificity of action by examining the ability of the type 1 IGF receptor antibody, alpha-IR3, to inhibit IGF action. Small ovarian cortical biopsies were obtained at laparoscopy, from 45 premenopausal women, with informed consent and local Ethical Committee approval. The tissue was divided and randomly allocated to 5 conditions. One piece was fixed immediately (control) and the others were cultured for 7 days with or without IGF-1 (1-100 ng/ml). Tissue was cultured on plate inserts using growth factor-reduced Matrigel. 18 biopsies were also allocated to 2 further conditions using alpha-IR3 in the presence or absence of IGF-I at 1ng/ml. After 7 days the tissue was fixed, serially sectioned and stained with haematoxylin and eosin. The health (atretic or non-atretic) and stage of development of follicles were assessed. The percentage of atretic follicles increased in culture, was reduced only by the highest concentration of IGF-1 (100ng/ml) and not affected by alpha-IR3 (1μg/ml). IGF-1 1ng/ml increased the proportion of follicles recruited from the primordial pool from 63 to 93 % (p< 0.0001, Chi-square) and increased the proportion of follicles entering the primary pool (p=0.017). The addition of alpha-IR3 to the system inhibited the increase in growing follicles (p< 0.0001, Fisher's exact test). In summary, these data confirm that IGF-1 has a significant positive effect on initiation of follicle growth in the human ovary. The attenuation of this effect by alpha-IR3 confirms that this action of IGF is indeed mediated via the type 1 IGF receptor.