A low-protein diet during pregnancy in the rat results in intrauterine growth restricted (IUGR) fetuses. The adaptive responses of the mother to low-protein diet and the mechanisms of IUGR in this model are not understood. In the present study, we report the maternal metabolic responses to protein restriction and their impact on growth, carcass composition, and translation initiation in the fetus. Pregnant Sprague-Dawley rats were pairfed either a 6% protein (LP, n ϭ 7) or a 24% protein (NP, n ϭ 7) diet from conception until delivery. Plasma amino acids and urea levels and rate of oxygen consumption were measured sequentially through pregnancy. Translation initiation factors eIF2␣, Ser 51 phosphorylated eIF2␣, eIF4E, phosphorylated eIF4E, and 4E-BP1 were quantified in the maternal and fetal muscle and liver. Protein restriction resulted in higher rate of oxygen consumption (p Ͻ 0.01), lower plasma branched chain amino acid (p Ͻ 0.05) in the mother, and lower plasma histidine levels (p Ͻ 0.05) in the fetus. Plasma urea nitrogen was lower in the LP group throughout gestation. The phosphorylated 4E-BP1 (␥ form) in the maternal liver was 4-fold higher in the LP group. The phosphorylated eIF2␣ was higher in the livers of IUGR fetuses. We speculate that the lower plasma branched chain amino acids in the mother during early pregnancy may be due to a lower rate of protein turnover in the LP group. The mechanism of increased energy consumption due to protein restriction remains unclear. The data on translation initiation factors suggest a higher rate of protein synthesis in the maternal liver and a lower rate in the fetal liver in response to protein restriction. Epidemiologic studies in humans have shown a significant correlation between intrauterine growth restriction (IUGR), low birth weight, and a number of morbidities in adult life (1-3). A number of studies in animals, particularly rat, have confirmed these findings (4 -7). Protein restriction during pregnancy in the rat has often been used to induce IUGR in the fetus. In the present study we have examined the adaptive responses of the mother to protein restriction during pregnancy. Specifically, we have examined the temporal changes in plasma amino acid and urea concentration, and changes in oxygen consumption in the mother.Adaptive responses to normal pregnancy in humans and animals are characterized by hypoaminoacidemia, a lower rate of urea synthesis, and a lower rate of protein turnover as compared with nonpregnant controls (8, 9). Studies in rat have shown an increase in fractional rate of protein synthesis in the liver during pregnancy. No significant effect of pregnancy on protein synthesis in skeletal muscle was observed in this study (10). Dietary restriction of protein to 9% in pregnant rat results in specific changes in plasma amino acid concentration, i.e. an increase in glycine and glutamine concentration, and a decrease in branched chain amino acids and threonine concentration (11). However, these studies were not controlled for energy intake, since ...