We evaluated the effect of vaccination with the SAG1 protein of Toxoplasma gondii against congenital toxoplasmosis in mice with different genetic backgrounds. In BALB/c mice (H-2(d)), vaccination reduced the number of infected fetuses by 50% and was associated with a mixed type 1 and type 2 immunity. In CBA/J mice (H-2(k)), vaccination increased the number of infected fetuses by 50% and was associated with a predominant type 2 response. Our results indicate that the effect of vaccination with SAG1 is controlled by the genetic background of the mouse.