In order to study the possible role of EGFR receptors in the bitch reproductive process, we have analyzed the expression pattern and localization of EGFR receptors and some of their ligands epidermal growth factor (EGF), neuregulin (NRG), amphiregulin (AREG), in the uterus during the estrus cycle using immunohistochemistry. The immunostaining for receptors and ligands of EGFR/ligand system was confined to membrane and cytoplasm of the target cells. Variations were observed, not only at the different stages of the estrous cycle, but also in the different tissue compartments of the uterus. However, it was detected that the immunostainings for NRG and AREG in the different cells do not show important differences at stages of the estrus cycle. In the luminal epithelium, strong immunostaining for ErbB1/HER1, ErbB2/HER2, ErbB4/HER4 and EGF was found at estrus. In the glandular epithelium, strong immunostaining for ErbB4/HER4 was observed at diestrus, while strong immunostaining for EGF was detected in both of estrus and diestrus. ErbB3/HER3 immunoreactivity in the stromal cells was higher at diestrus and anestrus, while ErbB4/HER4 immunoreactivity was lower at anestrus. In the myometrium, the highest levels of immunoreactivity of ErbB2/HER2 were found at estrus, while ErbB3/HER3 immunoreactivity was higher at anestrus. EGF immunoreactivity was lower at anestrus compared to other stage of cycle. Altered EGFR/ligand system expression during the estrus cycle suggests this growth factor system is a potent regulator of proliferation and differentiation events during preparation for implantation of bitch uterus.