Two different hormonal regimens to induce pseudopregnancy resulted in a pronounced increase in the susceptibility of the murine uterus to intraluminal injections of Listeria monocytogenes. Preimmunization, which profoundly augments systemic listeria resistance, had no effect on this increased uterine susceptibility. Anti-listerial responses in other organs were unaffected by pseudopregnancy. Animals manifesting increased susceptibility formed distinct uterine swellings in response to the combination of hormones and uterine listeria. These swellings correspond to previously described deciduoma and closely mimic the decidualized endometrium of pregnancy. The nature of the defective response to listeria was investigated by immunocytochemistry. Increased bacterial titers were correlated with an inability of macrophages and T lymphocytes to reach tissue listeria in discrete regions of deciduoma-bearing uteri. Control uteri showed a normal granulomatous pattern of inflammation. These findings closely parallel previous findings in the murine decidua basalis and suggest that properties of decidualized endometrial stromal cells regulate local immune responsiveness.