Interferon-gamma (IFN-gamma) is a potent proinflammatory cytokine that modulates hematopoietic cell maturation, differentiation, activation, and apoptosis, To evaluate the postulate that locally produced IFN-gamma could influence uterine hematopoietic cells, specific protein was detected by immunohistochemistry and messenger RNA (mRNA) was identified by in situ hybridization in cycling and pregnant mouse uteri, In cycling uteri, IFN-gamma was limited to luminal and glandular epithelial cells during the estrus phase of the cycle. In pregnant uteri, IFN-gamma was prominent at early (gestation day 6-10) and late (gestation day 18) stages. IFN-gamma-producing cells identified by in situ hybridization included uterine epithelial cells, natural killer cells, macrophages, placental trophoblast cells, and cells in the degenerating metrial gland, Collectively, the data indicate that programming of immune and other cells via autocrine and paracrine pathways could be achieved by locally produced IFN-gamma, and suggest that uteroplacental IFN-gamma may be most influential during early and late stages of pregnancy.