We have previously shown that decidua is the major site of transforming growth factor-alpha (TGF-alpha) gene expression at the feto-maternal interface during the early stages of pregnancy in the rat. The present study was undertaken to determine whether the presence of TGF-alpha mRNA in the decidua was in direct response to a signal derived from the conceptus. We therefore used the model of pseudopregnancy in rat, inducing decidualization in the absence of a conceptus. TGF-alpha mRNA expression was examined using Northern blot analysis, and TGF-alpha peptide was localized using immunohistochemistry. Pseudopregnancy was produced through standard hormonal priming followed by an artificial stimulus of intrauterine sesame oil or PBS to induce decidualization. Northern blot analysis demonstrated TGF-alpha mRNA expression specifically in the deciduoma beginning on the day of decidual stimulus (Day 4), increasing on Day 6, and continuing through Day 14. In contrast to decidua of normal pregnancy, an additional transcript of 3.0 kb was present in the deciduoma. Immunohistochemistry of tissues from Day 9 of pseudopregnancy revealed specific cytoplasmic immunoreactivity in the majority of stromal type decidual cells of the antimesometrial area, whereas mesometrial decidual cells were not immunoreactive. The results indicate that the induction of decidual TGF-alpha gene expression is not in direct response to a signal derived from the conceptus but is a de novo event associated with the decidual reaction, and that the resulting TGF-alpha peptide is present in the majority of stromal type antimesometrial decidual cells. These findings also suggest that TGF-alpha could be playing a role in proliferation and/or differentiation of the decidua.