Transforming growth factor beta (TGF-) plays a role in enterocyte proliferation control, cell differentiation and immune regulation via binding to specific TGF- receptors (TGF- R) in the intestinal epithelium. Endogenous TGF- production is low in the perinatal period but the fetal enteral diet, amniotic fluid, and postnatal colostrum also contain TGF- ligands. It is not clear however, whether luminal TGF- receptors are present and functional at this critical time. We studied intestinal TGF- receptors by immunohistochemistry during the last 20% of gestation in pigs and in chronically catheterized fetuses following exposure to colostrum, milk and amniotic fluid (control). In fetal pigs, the TGF- Rs were predominantly localized to the crypt epithelium but staining intensity increased markedly just before term and shifted to the villous epithelium in newborn pigs, concurrently with marked increases in villous heights and crypt depths (+100-200%, P < 0.05). In contrast to previous observations in term newborn pigs, fetal pigs did not show any milk-induced change in TGF- receptor densities or localization although a moderate increase in villous height was observed, relative to control (+25-50%, P<0.05). We conclude that intestinal TGF- receptor density and localization are immature and unresponsive to TGF- containing milk diets in prenatal pigs. Immaturity of TGF- mediated immune regulation may play a role in the increased sensitivity of preterm neonates to diet-induced intestinal inflammatory disorders.