The role of the strain of Toxoplasma gondii in genetic control of resistance against acute infection with T. gondii was studied with 2 strains of T. gondii, which differ in their virulence and genotype. Following peroral infection with 10 cysts of the C56 strain, C57BL/6 (H-2b) and C3 H/HeN (H- 2(k)) mice died significantly earlier than BALB/c mice (H-2(d)) mice, although all of the mice eventually died of acute toxoplasmosis from 10 to 23 days after infection. There was no significant difference in time to death between C57BL/6 mice and C3H/HeN mice. In peroral infection with 100 cysts of the less virulent ME49 strain, all C57BL/6 mice died of acute toxoplasmosis from 7 to 10 days after infection. C57BL/6 mice died significantly earlier following infection with the ME49 strain than with the C56 strain, whereas all C3H/HeN mice infected with the ME49 strain survived as did BALB/c mice. These results indicate that genetic control of resistance against acute infection with T. gondii differs depending on the strain of T. gondii.