Mice inoculated weekly with Plasmodium berghei sporozoites while under treatment with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, developed protective immunity against subsequent challenge with this parasite. The percentage of mice protected was similar whether DFMO alone (55%) or DFMO + chloroquine (65%) was used. With chloroquine alone, only 12% of mice were protected. This protection was long-lasting (at least six months). The immunity protected against sporozoites but not against erythrocytic form inoculation. It is suggested that this protection is induced by antigens released from exoerythrocytic schizonts whose further development is inhibited by DFMO.