It is shown here that B cells, in addition to CD4+ T cells, are necessary for the development of protective immunity to Plasmodium chabaudi chabaudi (P. chabaudi) in mice. Reconstitution of severe combined immunodeficient (SCID) mice with immune or normal CD4+ T cells protected the majority of mice against an otherwise lethal challenge but the mice were unable to clear their parasitemias. By contrast, transfer of the same T cell populations into athymic nu/nu mice enabled the recipients to control and clear their infections, immune CD4+ T cells being most effective. Furthermore, SCID mice given CD4+ T cells from immune and normal donors simultaneously with immune B cells also could eliminate their infection. Clearance of parasitemia correlated with the presence of malaria-specific antibodies in the serum. The role of B cells and CD4+ T cells in the protective immune response to P. chabaudi is discussed.