Under experimental conditions, Plasmodium berghei infection causes cerebral malaria (CM) in susceptible strains of mice such as C57BL/6 and CBA/Ca, whereas BALB/c or DBA/2J strains serve as a model for CM-resistant mice. The aim of the present study was to investigate the susceptibility of the CF1 mouse strain, carrying a spontaneous mutation of the mdr1a gene, to infection with Plasmodium berghei ANKA (PbA). The mdr1a gene codes for P-glycoprotein (P-gp/ABCB1), an efflux pump that is one of the major components of the blood-brain barrier. P-gp effluxes a broad range of xenobiotics from the brain to blood, preventing accumulation and toxicity in the central nervous system. CF1 mdr1a (−/−) mice are used to investigate drug transport by efflux pumps. Because many antimalarial agents are effluxed by P-gp (mefloquine, quinine), it was important to determine whether CF1 mice can develop cerebral malaria to predict drug toxicity during cerebral malaria. Our work showed that CF1 mdr1a (−/−) mice are susceptible to PbA. CF1 and C57BL/6N mice (the reference strain) infected with PbA have similar profiles with regard to clinical signs, brain histological lesions, and brain macrophagic activation observed by immunohistological methods.