The luteal microenvironment is thought to direct the function of resident immune cells to facilitate either luteal function or regression. To determine if luteal cells from functional (Days 10–12) and regressing (8 h after administration of prostaglandin F_2alpha) corpora lutea (CL) induce different responses in γδ T cells, luteal cells were cocultured with autologous γδ T cells isolated from peripheral blood. Proliferation, functional phenotypes, and cytokine synthesis were analyzed by flow cytometry. To determine if the luteal cells from functional CL induce hyporesponsiveness in γδ T cells, γδ cells were cocultured with midcycle luteal cells and further stimulated with concanavalin A. Coculture of γδ cells with midcycle luteal cells did not inhibit concanavalin A-induced proliferation. In a proliferation assay, luteal cells from midcycle CL predominantly induced proliferation of γδ WC1⁻ cells (P < 0.05), while luteal cells from regressing CL predominantly induced proliferation of γδ WC1 cells (P < 0.05). Analysis of intracellular cytokines indicated that midcycle luteal cells increased the proportion of γδ cells containing interleukin 10 (P < 0.05), but reduced the proportion of γδ cells containing interferon gamma (IFNG; P < 0.05). There were no changes in the proportions of γδ cells synthesizing interleukin 4 or tumor necrosis factor. Unexpectedly, coculture of γδ cells with luteal cells from regressing CL had no effect on any of the cytokines analyzed. These data support the hypothesis that the function of resident T cells is differentially modulated depending on the status of the CL.