ABSTRACT: Major burns induce immune complications, which are associated with myeloid cell activation by ill-defined mechanisms. Although γδ T cells have been shown to be important in postinjury inflammation and wound healing, their role in the regulation of myeloid cells remains unknown. To study this, wild-type (WT) and γδ T cell–deficient (δTCR-/-) mice were subjected to major burn (25% total body surface area, third degree) or sham treatment. At 3 days thereafter, skin samples were assayed for cytokine content or used to isolate single cells that were used for myeloid cell characterization by flow cytometry. The number of CD11b+ myeloid cells increased by approximately 75% in the wound skin of WT mice. This influx was caused by increased myeloid-derived suppressor cells (CD11b+ GR1+) whose numbers increased 19-fold compared with those of sham skin. In contrast, macrophage (MØ; CD11b+ F4/80+) numbers decreased by approximately 50% after burn. In δTCR-/- mice, burn increased the myeloid cell numbers approximately 5-fold. The increase in myeloid cells at the injury site of δTCR-/- mice was caused by both a myeloid-derived suppressor cell (50-fold) and a MØ (2-fold) influx. Burn increased skin cytokine levels for a number of prototypic inflammatory cytokines (interleukin 1β, interleukin 6, tumor necrosis factor-α, macrophage inflammatory protein [MIP] 1β, etc). Tumor necrosis factor-α, MIP-1α, and MIP-1β levels were further elevated (2- to 3-fold) in the injured skin of δTCR-/- mice compared with those of WT mice. In conclusion, these data show that γδ T cells regulate myeloid cell infiltration of the wound site and act to quell inflammation, thereby promoting the transition to the proliferative phase of wound healing.