To determine the effects of ovariectomy and 17 beta-estradiol (E2) on serum IGF-I and its binding proteins, female Sprague-Dawley rats, aged 95 days, were divided into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and 5000 ng (high dose) E2/kg body wt./day, respectively and the others were given solvent vehicle. Ovariectomy resulted in a significant increase in serum IGF-I (P < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals that received low-dose E2 while high-dose E2 reduced serum IGF-I levels below those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low-dose E2 restored, and high-dose E2 reduced serum IGFBP-3 levels compared to the levels for the sham-operated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot data. The changes in the levels of IGF-I and its binding proteins were accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers and loss of cancellous bone that were attenuated by E2 administration. We conclude that there is a possible role for IGF-I in the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.