The combined stress of protein-energy malnutrition (PEM) and exposure of the jejunum to pathophysiological (0.5 mM) levels of a bacterial metabolite, deconjugated bile salts, led to alterations not apparent with either stress alone. Perfusion of the jejunum of PEM rats with 0.5 mM deoxycholate (DCh) and a 40,000 dalton macromolecular tracer, horseradish peroxidase, led to higher serum horseradish peroxidase levels than were seen in PEM rats not exposed to DCh or in well-nourished controls treated with DCh. Semiquantitative cytochemical analysis indicated an increased number of villi with horseradish peroxidase penetration in PEM rats treated with 0.5 mM DCh. DCh perfusion of PEM rats also produced fine structural damage to epithelial cells not apparent in other preparations. And, perfusion with 0.5 mM cholate only produced sodium secretion in PEM rats. These observations in an animal model of PEM suggest that malnourished children with a colonic type of bacterial overgrowth of the small bowel may attain increased levels of foreign antigens or toxins from the intestinal lumen.