DBA/2 (H-2^d) mice are known to be more resistant than C57BL/6 (B6, H-2^b) mice to the non-lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8⁺ T cells, are known to be somewhat lower in DBA/2 mice than in other strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 × B6)F₁ (BDF₁, H-2^b/d) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF₁ mice were also found to experience a marked expansion of interleukin (IL)-2Rβ⁺ CD3^int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220⁺ T cells) was also marked in DBA/2 and BDF₁ mice. The majority of B220⁺ T cells were γδ T cells and these T cells were double-negative CD4⁻ CD8⁻. More importantly, the production of immunoglobulin M (IgM)-type anti-DNA autoantibody was also higher in DBA/2 and BDF₁ mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody-producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non-lethal 17XNL strain of P. yoelii.