Progesterone is known to enhance epidermal growth factor (EGF)-mediated cellular responses by up-regulating EGF-receptor (EGF-R) expression. Ligand activation of EGF-R in turn has been shown to activate cytoplasmic stores of the STAT3 (signal transducer and activator of transcription) transcription factor, whereupon it translocates to the nucleus. The aim of this study was to examine the ontogeny of STAT3 protein expression in the decidualized mesometrium (i.e., decidua basalis) of the rat during pregnancy and its interactions with the progesterone-progesterone receptor (PR) system. STAT3 was abundantly expressed in the cytosolic fraction of decidual homogenates throughout pregnancy; however, expression in the particulate fraction (assumed to reflect primarily nuclear accumulation) was reduced more than 75% on Days 12–17 than it was on Days 8 and 10. This pattern of expression parallels the decline in EGF-R and coincides with decidual regression. Treatment of pregnant rats with antiprogestin (RU486) in early pregnancy resulted in an 80% reduction in cytosolic abundance of STAT3 within 12 h, but it had no influence on STAT3 abundance in the particulate fraction. Immunoprecipitation of decidual lysates with PR or STAT3 antibodies resulted in coprecipitation of STAT3 and PR, respectively. These observations suggest that STAT3 expression is a prevalent feature of progesterone action, and that STAT3 and PR interactions represent a convergence of diverse signal transduction pathways in the decidualized mesometrium during pregnancy.