CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.