The epidermal growth factor (EGF) plays a crucial role in the control of uterine cell proliferation, growth and differentiation. This study was designed to investigate the spatiotemporal expression pattern and localization of the EGF receptor/ligand system during the process of uterine involution using immunohistochemistry. Our results indicated that the expression of the ErbB/HER receptors and their ligands varied with structural changes in the uterus at different days of involution. Supranuclear punctate ErbB1 immunostaining was observed in the luminal and glandular epithelial cells and endometrial fibroblasts. Moderate ErbB2/HER2 immunoreactivity was observed in the lateral membrane and cytoplasm of the epithelial cells on the 1st, 3rd and 5th days and was decreased on the other days of involution. The amount of nuclear and cytoplasmic ErbB3/HER3 and ErbB4/HER4 immunostaining remained constant throughout the postpartum period. The EGF immunoreaction was weak in the luminal and glandular epithelium throughout the involution period. Although the cytoplasmic AREG immunoreactivity in the glandular epithelium was stronger on the 1st and 3rd days compared with the other days of involution, NRG1 immunostaining was weak on the 1st and 3rd days and was moderate in the apical cytoplasm on the 10th and 15th days of involution. The macrophages displayed strong cytoplasmic immunoreactivity for ErbB3/HER3, ErbB4/HER4, EGF, AREG and NRG. Strong, moderate and weak immunostaining for ErbB2/HER2, ErbB4/HER4 and other proteins (ErbB1, ErbB3, AREG and NRG), respectively, was present in the myometrial smooth muscle cells. These findings support the hypothesis that the EGFsystem plays a role in the development of various physiological changes associated with uterine involution.