We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the lastweekofpregnancy)at21.5dpostcoitumexhibitincreased -cell mass. This alteration is correlated with increased insu- linemiaandtotalpancreaticinsulincontent,apatternsimilar 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, GH, and 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 in- creases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I ex- pression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was dimin- ished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver andpancreaticmRNAexpressionofIGFBP-1werefoundtobe normal in undernourished fetuses, whereas the serum con- centration 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 undernour- ished fetuses the increased -cell mass can be related to the stimulation of replicative -cell response due to locally in- creased pancreatic IGF-I mRNA; this effect is perhaps poten- tiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression. (Endocrinology 146: 1364-1371, 2005)