To determine whether insulin-like growth factor-I (IGF-I) plays a role in rabbit corpus luteum (CL) physiology the authors examined: IGF-I expression, the effect of IGF-I on progesterone (P) production in vitro, and the interaction of IGF-I with estradiol, the primary luteotropin in the rabbit. Northern blot analysis revealed that IGF-I mRNA is present in the rabbit CL throughout pseudopregnancy. An intact ovarian in vitro perfusion model and dispersed luteal cell culture were used to determine the effects of IGF-I on P production and interactions with estradiol. IGF-I significantly stimulated P production compared to control medium by the isolated, intact perfused rabbit ovary and by dispersed, cultured luteal cells. Estradiol alone did not stimulate P production in vitro. Estradiol did augment IGF-I-stimulated P production in the intact perfused ovary and in luteal cell culture. These findings support a role for IGF-I in rabbit CL P production.