The molecular mechanisms by which endometriosis persists in locations outside the uterus are unclear. Recently, the epidermal growth factor receptor (EGF-R) has been postulated to have a role in the disease process of endometriosis. To explore this, we determined the levels of EGF-R protein and messenger ribonucleic acid (mRNA) expression in endometriotic tissues and compared the levels to that of eutopic endometrium. Using rabbit anti-EGF-R antibody, we found more intense immunohistochemical staining for EGF-R in glandular cells than in stromal cells of both endometriomas and endometriotic implants. No difference in staining intensity was noted between endometriotic tissues and eutopic endometrium. A ribonuclease protection assay was used to determine mRNA levels for EGF-R. PhosphoImager analysis revealed the following levels of mRNA for EGF-R; eutopic endometrium, 1.00 +/- 0.27 (arbitrary units; mean +/- SEM; n = 6 patients); cyst walls of endometriomas, 0.21 +/- 0.12 (n = 10 patients); endometriotic implants, 0.29 +/- 0.13 (n = 9 patients); and pelvic adhesions, 0.03 +/- 0.03 (n = 5 patients). Endometriotic tissues had significantly less mRNA for EGF-R than eutopic endometrium (P < 0.05, by Newman-Keuls test). Our findings support the hypothesis that EGF-R may be associated with the disease process of endometriosis.