Gastrointestinal epithelium produces surface-active material closely related to that produced by pulmonary alveolar type II epithelial cells. This material includes surfactant-associated protein A (SP-A) which may play a role in gut defense mechanisms. Rubio et al. (J Biol Chem 270:12162, 1995) first demonstrated SP-A in the large and small intestines but not in the stomach of the adult rat. To ascertain the ontogeny and localization of gastrointestinal SP-A we investigated the expression of mRNA in fetal rat gut using RT-PCR with nested primers. Amplification of the cDNA yielded appropriately sized SP-A bands (372 base pairs) in the 17-day fetal rat stomach and intestine; 18-day fetal rat stomach and intestine; 20- and 21-day fetal rat stomach, small intestine and large intestine. These findings were correlated with SP-A expression in the adult rat lung as a positive control and the lack of SP-A expression in the adult rat kidney as a negative control. This is the first documentation of SP-A expression by the fetal rat gastrointestinal tract. Expression of pulmonary SP-A by the fetal rat was reported at gestational day 15.5 by in situ hybridization(Meneghetti, et al. J Histochem Cytochem 44:1173,1996) and at gestational day 13 by RT-PCR (Wang, et al. Am J Respir Cell Mol Biol 10:222, 1994). Our on-going studies are aimed at quantitative analysis of the temporal and spatial profile of SP-A expression in the rat G.I. tract and its possible role in gut defenses.