The toxin of Vibrio cholerae increases the activity of adenyl cyclase in cell membranes. Interaction between intestinal cell membranes and the toxin of V. cholerae leads to the profuse secretory activity seen in choleraic diarrhea. Lipid-containing extracts of various tissues were found to inhibit the activity of cholera toxin; the highest amounts of the inhibitory factor were found in brain. The inhibitor has properties similar to those of gangliosides. The effect of cholera toxin on intestinal loops of rabbits and epididymal fat cells of rats was neutralized by purified ganglioside. The results suggested that fixation to gangliosides may play a role in the binding of cholera toxin to cell membranes.