Striking differences in the resistance to P. chabaudi infection among different inbred mouse strains have previously been correlated with the level of both the spontaneous and the infection-induced enhanced level of NK cell activity. We have examined this putative correlation in individual animals of backcross progeny derived from A/J (malaria-susceptible, low NK cell activity) and B10.A (malaria-resistant, high NK cell activity) progenitors. We have found that NK cell activity and resistance to malaria segregated independently. Furthermore, C57BL/6-bg/bg mice which are deficient in NK cell activity were found to be as resistant to malaria as their heterozygous C57BL/6-bg/+siblings. We conclude that low NK cell activity, characteristic of A/J strain mice, is not a sufficient determinant of the exquisite susceptibility of these animals to infection with Plasmodium chabaudi.