Because the role of cell-mediated immunity (CMI) in the resolution of blood-stage malaria remains unclear, we examined the question of whether mice completely lacking Ab-mediated immunity (AMI) but possessing some CMI can resolve experimental malaria previously reported not to require AMI for resolution. Severe combined immunodeficient mice reconstituted with enriched immune T cells (< 0.5% B220+ cells) suppressed acute Plasmodium chabaudi adami parasitemia, suggesting that T, but not B, cells are required to clear this form of malaria. In addition, JHD mice, which are a definitive model of B cell deficiency, were also shown to resolve P. chabaudi adami, Plasmodium vinckei petteri and Plasmodium chabaudi chabaudi malaria. These observations collectively establish that CMI alone can mediate the clearance of acute malaria caused by these subspecies of Plasmodium. Moreover, the protective cell-mediated immune response involved depends upon CD4+ T cells because JHD mice treated with anti-CD4 mAb do not resolve their infections. These results suggest that evaluation of immunization regimens to activate CD4+ T cell dependent cell mediated immunity against Plasmodium falciparum may be appropriate.