Immunohistochemical studies were performed using specific antibodies to epidermal growth factor (EGF) and EGF receptor to determine their presence and cellular localization in the human ovary during follicular growth and regression. There was no immunostaining for EGF or EGF receptor in primordial follicles. In the preantral follicle stage, immunostaining for EGF and EGF receptor was observed only in the oocyte. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. In the antral follicle stage, immunostaining for EGF and EGF receptor became apparent in the granulosa and theca interna cell layers, without appreciable staining in the surrounding stromal cells. The immunostaining for EGF and EGF receptor in the granulosa cells and theca interna cells persisted in preovulatory follicles and corpus luteum, and intensified in the midluteal phase. The stromal cells surrounding the corpus luteum were negative for EGF and EGF receptor staining. In the regressing corpus luteum, immunostaining for EGF and EGF receptor was present in the peripheral lutein cells adjacent to the central core of scar tissue, but absent in the scar tissue of the central core. Corpus albicans showed no staining for EGF and EGF receptor. By contrast, the stromal cells surrounding the corpus albicans in the cortex region demonstrated intense staining for EGF and EGF receptor, while the stromal cells surrounding the corpus albicans in the medullary region were negative for immunostaining. In the case of atretic follicles, the theca interna cells showed intense staining for EGF and EGF receptor, but immunostaining in the scattered granulosa cells was negligible. This is the first study to demonstrate a remarkable change in the expression of EGF and EGF receptor in the oocyte, granulosa cells, thecal cells, and surrounding stromal cells over the course of follicular growth and regression. The results obtained support EGF participation in oocyte maturation and in follicular growth and atresia. The intense immunostaining for EGF and EGF receptor observed in the theca interna cells in atretic follicles and the stromal cells surrounding corpus albicans in the cortex region raises the possibility of EGF involvement in transformation of thecal cells into stromal cells. Furthermore, the cell type-specific simultaneous expression of EGF and EGF receptor in follicular and stromal compartments in the various stages of follicular development suggests that an autocrine mode of EGF action may exist to regulate follicular growth and regression in the human ovary.