The inhibition of the activity of enterotoxins by bismuth salts was assessed in laboratory models. In the Y-1 adrenal cell tissue culture system, a commercial preparation containing bismuth subsalicylate reduced the activity of crude toxin from Vibrio cholerae by 10(4)-fold as compared with the activity of controls. Similar results were obtained with use of the adult rabbit ligated intestinal loop model. The preparation failed to affect crude Escherichia coli or cholera toxin activity once these toxins had become bound to intestinal mucosa. Pretreatment of ligated loops with the preparation reduced the fluid accumulation mediated by crude E. coli and cholera toxins by 78% and 91%, respectively. Bismuth subsalicylate and the complex vehicle of the preparation also inactivated toxin; however, bismuth subsalicylate was more effective when combined with the vehicle. Bismuth subcarbonate failed to inhibit fluid accumulation in ligated loops. Preparations containing bismuth subsalicylate may be effective in the prevention of diarrhea mediated by toxigenic E. coli.