Asexual blood forms of malaria parasites are microaerophilic and sensitive to oxidant stress. Plasmodium falciparum and some other species of malaria parasites undergo schizogony attached to endothelial cells of postcapillary venules, where oxygen tensions are low. Acquired immune responses to all forms of malaria parasites so far investigated are thymus dependent. Animals deprived of T lymphocytes do not recover from the infections and cannot be immunized against malaria parasites. In contrast, animals unable to make antibodies recover normally from some primary infections, e.g. with Plasmodium chabaudi, and when rescued by chemotherapy from other species of malaria parasite develop lasting, nonsterile immunity. Immunity to malaria can be transferred in mice by T lymphocytes of the Ly1+ phenotype, but transfer of B lymphocytes together with this T-cell subset increases the effectiveness of immunity to Plasmodium yoelii. Thus, antibodies facilitate recovery from some primary malaria infections and increase the effectiveness of cell-mediated immune responses in these infections. Mice of the A strain are highly susceptible to malaria and are unable to increase the number of mononuclear cells in the spleen during the course of the infections. It is postulated that T lymphocytes responding to parasite antigens release factors that stimulate the proliferation of effector cell precursors and their recruitment into the red pulp of the spleen. In this site, the liver and probably the peripheral circulation, effector cells bind to the surface of parasitized erythrocytes and are activated to release superoxide (O2-). The consequent exposure to oxidant stress can lead to degeneration of parasites in erythrocytes. This effect on the parasites can be prevented by agents chelating metals, which suggests that iron-catalyzed lipid peroxidation and consequent K+ loss, or inactivation of metal-containing enzymes, may be the mechanism by which oxidant stress kills the intracellular parasites. Antibodies on the surface of schizont-infected cells could facilitate binding of effector cells and trigger O2- release, thereby acting synergistically with cell-mediated immunity. Inherited traits, such as abnormal hemoglobins and G-6-PD deficiency, and acquired cell-mediated immunity both subject malaria parasites to oxidant stress and may reinforce one another, increasing the chances of survival of children bearing these traits during the dangerous years of first exposure to malaria in areas where the disease is endemic.