Insulin-like growth factor-I (IGF-I) may regulate small bowel growth. Analyses here in ad libitum-fed, fasted, and refed rats demonstrate that during fasting and refeeding changes in jejunal mass correlate with changes in serum IGF-I and jejunal IGF-I mRNAs. These data indicate that circulating and locally expressed IGF-I contribute to nutrient regulation of jejunal mass. During refeeding, jejunal IGF binding protein 3 (IGFBP-3) mRNA abundance was reduced relative to that of IGF-I, possibly amplifying enterotrophic actions of IGF-I. Localization of IGFBP-3 to subepithelial cells in lamina propria of jejunum indicates that IGFBP-3 derived from lamina propria may modulate IGF-I action on adjacent epithelium. Ileum differed from jejunum in that refeeding did not increase bowel mass or IGF-I mRNA to ad libitum values. Differences in exposure to luminal nutrient may underlie distinct responses of the two segments. Rats fed elemental diet intravenously showed reduced jejunal mass but not reduced jejunal IGF-I mRNA compared with rats fed oral elemental diet. Elemental nutrient given intravenously or orally therefore does not differ in effects on jejunal IGF-I expression. Complex luminal nutrient may, however, regulate jejunal IGF-I expression.