The mammalian ovulatory process is a fairly complex succession of events that leads to the release of a competent oocyte. The luteinizing hormone (LH) triggers the cascade of events, which starts with the production of secondary messen- gers in the follicular wall and ends with the release of a fertilizable oocyte. Most of these events can be reproduced using in vitro models, which offer a wide range of possibilities for study strategies. Although it is accepted that epidermal growth factor receptor (EGFR) activation is required for transmission of the LH-initiated signal, we hypothesized that LH receptor activation might also play a role in oocyte meiotic resumption and cumulus cell response, because the current mouse preantral follicle in vitro model expresses functional LH receptor. To separate the LH-mediated response and the epidermal growth factor (EGF)-mediated response (following LH stimulus), in vitro-grown mouse ovarian follicles were stimulated for ovula- tion with a combination of human chorionic gonadotropin (hCG) plus galardin (inhibitor for the release of endogenous EGF-like factors) or hCG plus galardin plus EGF. Results suggest that the stimulation provided by LH (hCG) is insufficient to induce a maximum oocyte meiotic resumption and that EGFR activation is also required. Analysis of transcript levels of Egfr, Ereg, Cyp19a1, Hsd3b1, Adamts1, and Has2 in cumulus cells further indicate that the triggers for the EGFR cascade preserve the expression profile of the studied transcripts. Therefore, it is proposed that within this in vitro mouse model, EGF signaling during ovulation might protect the cumulus cells from the potential luteinizing effects of LH. © 2011 by the Society for the Study of Reproduction, Inc.