The administration of clindamycin to hamsters induces a lethal enterocolitis as a consequence of toxins produced in the alimentary tract by Clostridium difficile. The lethal and cytopathic effects of C. difficile toxins are neutralized in vitro by C. sordellii antitoxin and hamsters may be protected against clindamycin induction of caecitis by passive immunization using C. sordellii antitoxin. To examine active immunization using C. difficile and C. sordellii toxoids, groups of male and female Syrian hamsters were immunized on two occasions and challenged by parenteral clindamycin. A concentrated C. difficile toxoid protected 90% of females and 78% of males; the degree of protection per group decreased with dilution of the toxoid used for immunization. A similar degree of protection was observed in female hamsters immunized with a bivalent vaccine prepared from the partially purified toxins A and B of C. difficile. Immunization using a C. sordellii toxoid protected between 100 and 25% of females per group and between 50 and 12.5% of males per group.