As βδ T cells are believed to be involved in host defense against Leishmania major, the role of βδ T cells in immunity against this parasite was investigated. The growth of L. major was measured in αβ (T cell receptor [TCR] α -/-) and βδ (TCR δ -/-) TCR-deficient C57BL/6 mice and compared with growth in control (C57BL/6) mice. While TCR α -/- mice developed nonhealing lesions containing large numbers of parasites following L. major infection, TCR δ -/- and C57BL/6 mice effectively controlled the infection. Following in vitro stimulation, lymph node cells from C57BL/6 mice produced significantly more interferon (IFN)-γ than those from TCR δ -/- mice during early and late phases of infection; however, both produced similar levels of IFN-g at postinfection week 6. Culture supernatants from both TCR δ -/- and C57BL/6 mice contained interleukin- 4, at postinfection week 2 only. These results indicate that βδ CD3 T cells are not essential for mediating protection against cutaneous L. major infection in C57BL/6 mice.