Pregnancy-associated growth of maternal and fetal tissues is likely mediated by insulin-like growth factors (IGF). To study the effect of food restriction during pregnancy on the IGF system, pregnant rats either had free access to food (control) or were fed 60% of control food intake. Serum and liver samples were obtained throughout gestation. Serum IGF-I and growth hormone (GH) concentrations were measured by RIA, and IGF binding proteins (IGFBP) were characterized by Western ligand blotting and gel filtration chromatography. Weight gain of control dams was nearly twice that of restricted dams. Litter size was not significantly different; however, fetuses and placentas of restricted dams were 20% smaller than those of controls. Serum IGF-I concentrations on d 20 were 35 and 23% of d 5 concentrations in control and restricted pregnant rats, respectively. However, hepatic IGF-I mRNA did not differ between the treatment groups. A pregnancy-associated rise in serum GH was observed in control but not food-restricted dams. Insulin-like growth factor binding protein with apparent molecular retention of 38-42 kDa (IGFBP-3), 29-31 kDa and 24 kDa were apparent in serum of pregnant dams in early gestation; however, IGFBP-3 was no longer detected by Western ligand blot by d 15 of gestation. The decline in IGFBP-3 was accompanied by an increase in IGFBP-1 and -2, particularly in the serum of food-restricted dams. These data suggest that in food-restricted pregnant rats, serum IGF-I and IGF-I mRNA are insensitive to serum GH concentrations and are not regulated at the level of transcription.