Mice received a series of injections of formalin-killed merozoites (FKM) of exoerythrocytic stages of Plasmodium fallax prior to challenge with sporozoites of P. berghei. In one study 4 of 16 FKM-immunized mice never exhibited parasitized erythrocytes after 2 challenges of 10(4) P. berghei sporozoites each, while all control animals died with high parasitemias. FKM-immunized mice were as susceptible as control mice to infections initiated with parasitized erythrocytes. In a second study, 14 of 16 mice immunized via the intravenous (i.v.) or combined intramuscular (i.m.) and i.v. routes were immune to an initial challenge with 10(4) sporozoites, but were susceptible to a second challenge. Three injections of FKM via the i.m. or intraperitoneal routes did not elicit a protective response against sporozoite challenge. Sera harvested from FKM-immunized and control mice prior to challenge produced no visible CSP reaction with P. berghei sporozoites, nor was infectivity of sporozoites altered after incubation in sera, showing that SNA was absent. In additional experiments results were less encouraging. An attempt to repeat the result of the second experiment failed. Each of 5 mice which received the same number of FKM by a similar schedule became infected after sporozoite challenge. In an additional study the immunization schedule was increased from 3 to 7 injections of FKM and 40% of FKM-immunized mice resisted challenge. However, mice which had received FKM prior to sporozoite challenge consistently displayed an increased prepatent period compared with control animals. A department from methods of the more successful studies was necessitated in these later studies in which FKM were harvested from cell cultures maintained for longer periods of time.