Circulating prostaglandin E2 antibodies were produced in 12 rabbits immunized with prostaglandin E2-thyroglobulin conjugate and ulcers occurred in 10, usually in the stomach and less often in the small intestine. Immunization of rabbits with both prostaglandin E2 and 6-keto prostaglandin F1 alpha significantly increased the number of gastric ulcers compared with rabbits immunized with prostaglandin E2 alone. Gastrointestinal ulceration in prostaglandin E2-immunized rabbits was not prevented by oral enprostil. Gastrointestinal ulcers occurred as early as 6 wk after beginning immunization and often perforated with resulting fatality. Neither prostaglandin E2 antibodies nor ulcers developed in rabbits immunized with thyroglobulin vehicle (controls). Passive immunization of unimmunized rabbits with prostaglandin E2-hyperimmune plasma led to acute gastric ulcers within 9 days, whereas passive transfer of nonimmune plasma did not produce ulcers. This latter finding suggests that prostaglandin E2 antibodies per se were responsible for ulcer formation.