In this study, the role of NF-kappaB1 was examined during toxoplasmosis. While wildtype BALB/c mice generated protective responses, NF-kappaB1(-/-) mice developed Toxoplasmic encephalitis, characterized by increased parasite burden and necrosis in the brain. Susceptibility was primarily associated with a local decrease in the number of CD8(+) T cells and IFN-gamma production, while accessory cell function appeared intact in NF-kappaB1(-/-) mice. Consistent with these findings, T cell transfer studies revealed that NF-kappaB1(-/-) T cells provided SCID mice less protection than wildtype T cells. These results demonstrate an intrinsic role for NF-kappaB1 in T cell-mediated immunity to Toxoplasmagondii.