Interferon-tau (IFN-τ), the antiluteolytic signal produced by the trophoblast prior to implantation in ruminants, exhibits immunomodulatory properties. It stimulates the production of prostaglandin (PG) E₂ in bovine endometrial cells via the induction of cyclooxygenase-2 (COX-2). We previously demonstrated that preconditioning lymphocytes with PGE₂ increases the expression of granulocyte–macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes conceptus growth and survival. Our goal in the present study was to evaluate the impact of IFN-τ on the expression of GM-CSF in bovine peripheral blood lymphocytes (PBL) and endometrial epithelial and stromal cells. Changes in PGE₂ production and mRNA levels of COX-2 were also studied in PBL in response to IFN-τ. Gene expression was estimated by semiquantitative reverse transcription–polymerase chain reaction and Northern analysis. The expression of GM-CSF in PBL was stimulated by treatment with IFN-τ. Furthermore, GM-CSF mRNA levels were increased after preconditioning PBL for 3 days with IFN-τ, followed by a 12-h restimulation without IFN-τ. Inhibition rather than stimulation of PGE₂ production and COX-2 expression in PBL during treatment with IFN-τ suggests a direct effect on GM-CSF expression. Moreover, GM-CSF expression was stimulated in uterine stromal cells in response to IFN-τ. This study provides the first evidence for stimulation of GM-CSF expression by IFN-τ in both leukocytes and endometrial stromal cells. In view of the role of GM-CSF on fetal growth and survival, these results support the hypothesis that the conceptus mediates accommodation mechanisms in the uterus during early pregnancy by modulating the expression of beneficial cytokines at the fetomaternal interface.