The effect of exogenous IGF-I on the reproductive performance of female rats was examined by infusing either recombinant human IGF-I (400 micrograms/d; n = 19) or vehicle (n = 18) over a four-day period (the time of one reproductive cycle) beginning on the day following estrus. The females were exposed to male rats one day after the infusions had commenced, and were euthanized 15 d later. There was no treatment effect on serum progesterone levels at this time or on the number of fetuses. Furthermore, the number of corpora lutea were not different between the IGF-I and vehicle infused groups (15.8 vs. 14.8; P = 0.09). Total serum IGF-I concentrations, as determined with a polyclonal antiserum based RIA, were increased approximately three-fold in samples obtained 20 hr after commencing the IGF-I infusion. These samples were also analyzed for IGF-I with a monoclonal antibody based RIA previously shown to detect human, but not rat, IGF-I. By subtraction, the concentration of endogenous rat IGF-I was found to be approximately 60% higher in IGF-I-infused rats than in control rats. This increase was likely due to a reduced clearance rate of IGF-I from the circulation, caused by a marked induction of 42-46 kDa and 30-34 kDa IGF-I binding proteins observed in these samples with a ligand blot technique. The binding protein induction indicates that the infused IGF-I was bioactive. This induction may have attenuated the effects of IGF-I on ovarian function.