We examined the long-term effects of dietary protein restriction during rat pregnancy on serum IGF-I, serum IGF binding proteins, and liver IGF-I gene expression during postnatal development. Pregnant Wistar rats were fed ad libitum throughout gestation a normal (20% casein diet; P20 controls) or a low (5% casein; P5) protein diet. At birth, the pups from both P20 and P5 dams were cross-fostered to well nourished lactating dams, and litters (n = 5/dietary group) were reduced in size to 6 pups. After weaning (d 22), the pups were fed the control diet ad libitum. The pups were killed at 8, 22, and 63 d of age. Gestational protein restriction caused significant growth retardation and mortality in newborn pups. Despite food rehabilitation during the suckling period (d 0-22), body weight, tail length, and the weight of liver, heart, kidney, and brain in the P5 pups remained significantly reduced at 8 and 22 d (-17 to -35%) compared with control pups. At the same time, serum and liver IGF-I concentrations in the P5 pups (on d 8: 100 +/- 9 ng/mL and 11 +/- 1 ng/g, respectively; on d 22: 340 +/- 20 ng/mL and 42 +/- 3 ng/g) were lower than in age-matched controls (on d 8: 170 +/- 12 ng/mL and 26 +/- 2 ng/g; on d 22: 470 +/- 30 ng/mL and 73 +/- 5 ng/g), although liver IGF-I mRNA abundance was not affected. After long-term food rehabilitation (d 63), tail length and organ weight recovered, and serum and liver IGF-I concentrations were normalized. However, although the P5 rats had resumed a normal growth rate, their body weight remained lower than in the controls. There were no differences in serum IGF binding proteins 1-4, insulin, and GH concentrations between the groups at any age studied. These results suggest that reduction in serum IGF-I may contribute to the reduced somatic and organ growth observed in rats after gestational protein malnutrition, and further support a role for IGF-I in the control of catch-up growth.