Although it is well established that IGF-I is able to amplify the actions of FSH and LH on ovarian cells in vitro, little information is available regarding the effects of IGF-I on ovarian function in vivo. To address this question, rhesus monkeys whose spontaneous gonadotropin secretion was interrupted with a GnRH antagonist received continuous iv infusions of saline, IGF-I (240 microg/kg.d), or IGF-I (240 microg/kg.d) plus human GH (hGH) (200 microg/kg.d) 7 d before and continuing throughout a 15-d iv infusion of hFSH and hLH during which serum LH concentrations were maintained at 7-10 mIU/ml and FSH concentrations were incrementally increased every 3 d from 7.5 to 17.5 mIU/ml. Serum estradiol concentrations in saline-treated control animals did not differ (P > 0.05) from animals treated with IGF-I + hGH. In contrast, serum estradiol levels in IGF-I-treated animals were significantly less (P < 0.05) than those of control or IGF-I + hGH-treated animals. Serum androstenedione levels did not differ among the three treatment groups. Analysis of follicular fluids on the final day of gonadotropin infusion indicated that intrafollicular IGF-I concentrations paralleled serum IGF-I concentrations in all treatment groups. Measurement of the ratio of IGF-I to IGF-binding protein-3 in follicular fluids indicated that there was not a disproportionate increase in I-binding protein-3 in animals infused with either IGF-I alone or IGF-I + hGH. Concentrations of GH in follicular fluids of IGF-I treated animals were less than control animals suggesting that the diminished responsiveness of ovaries to FSH in the IGF-I treatment group may have been due to reduced GH.