The mechanisms whereby invasive enteropathogens, e.g., Salmonella typhimurium, induce intestinal secretion are largely unknown. Since these organisms penetrate the intestinal epithelium, disrupt the brush border, and evoke an acute inflammatory reaction, increased plasma filtration through a damaged, more permeable epithelium might contribute to the secretory process. To examine this possibility, the plasma-to-lumen clearance of two different sized molecules, [51Cr]albumin and [14C]mannitol, was measured in the in vivo rabbit ileal loop and in vivo rhesus monkey models of salmonellosis. In the rabbit ileal loop model, the clearance of neither molecule was increased when compared to cholera toxin-exposed loops. In the rhesus monkey, clearance of [14C]mannitol into the jejunum, ileum, and colon of Salmonella-infected animals did not differ from the observed in control animals. These data indicate that invasion of the intestinal mucosa by S. typhimurium has not substantially altered the permeability characteristics of the intestinal mucosa and that plasma filtration through a damaged, more permeable mucosa does not contribute to the Salmonella-induced intestinal secretory process.