Enterotoxigenic Bacteroides fragilis (ETBF) has been recently associated with watery diarrheal disease in livestock and young children. These strains of B. fragilis secrete an extracellular heat-labile protein toxin with a mess of approximately 20 kD. This toxin has been shown to have two major biological activities: stimulation of secretion in ligated intestinal segments in lambs and calves and alteration of the morphology of intestinal epithelial cell lines in vitro. In vivo the pathology of animal intestine exposed to an ETBF strain is disruption of the colonic epithelium with rounded, swollen surface epithelial cells. Similarly, in vitro intestinal epithelial cells derived from human colonic carcinomas become rounded and detach from neighboring cells after treatment with the ETBF toxin. These results suggest that the ETBF toxin is a secretory cytoskeleton-altering toxin. However, the contribution of the ETBF toxin to the pathogenesis of ETBF-associated diarrheal disease remains to be determined.