We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 days post coitum exhibit increased -cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, growth hormone, and insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the -cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-1 expression and islet IGF-1R content in undernourished fetuses, whereas hepatic IGF-1 expression and serum IGF-1 levels were decreased. No changes were observed in serum IGF-2 and its expression was diminished in undernourished pancreases and unchanged in the liver compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the -cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets compared with controls. In conclusion, in undernourished fetuses the increased -cell mass can be related to the stimulation of replicative -cell response due to locally increased pancreatic IGF-1 mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-1R content and pancreatic IGFBP-2 gene expression.