Hamsters were vaccinated with toxoids containing toxin A, toxin B, both toxins, or a preparation containing neither toxin of Clostridium difficile, the causative agent of antibiotic-associated cecitis in hamsters and pseudomembranous colitis in humans. To determine whether these vaccines would reduce the severity of antibiotic-associated cecitis, the hamsters were injected subcutaneously with clindamycin. Nearly all of the hamsters protected against neither toxin or only one toxin died. These animals developed enlarged hemorrhagic ceca and diarrhea, although the ceca from the animals immunized against toxin B were less hemorrhagic. The hamsters immunized against both toxins survived clindamycin treatment and had ceca of normal size and appearance. Concentrations of both toxins were lower in the ceca of the latter animals than in the unprotected animals. To determine the effects of either toxin alone on the animals, nonimmunized hamsters were injected with either purified toxin A, which produced enlarged ceca with moderate hemorrhaging, or partially purified toxin B, which produced hemorrhagic ceca of normal size. All of the hamsters injected with either toxin at concentrations found in the ceca after clindamycin treatment died. These results suggest that toxin A causes the water influx, that both toxins cause hemorrhaging to different extents in the ceca of hamsters with antibiotic-associated cecitis and that either toxin alone can cause death. These studies may help explain the etiology of pseudomembranous colitis in humans.