Although human uterus is known to contain epidermal growth factor (EGF) and its receptors, it is virtually unknown whether human fallopian tubes, which are an anatomical continuation of the uterus, also contain them. Therefore, the present studies investigated whether EGF and its structural and functional homolog, i.e. transforming growth factor-alpha (TGF-alpha), and their common receptor are expressed in human fallopian tubes. Human fallopian tubes contain major 10.5-kilobase (kb) and minor 6.0-kb receptor messenger RNA (mRNA) transcripts, a single 5.0-kb EGF mRNA transcript, and a single 170-kilodalton receptor protein. The transcripts, along with their corresponding proteins and TGF-alpha protein, are present in ciliated and nonciliated epithelial cells, tubal smooth muscle, vascular smooth muscle, and endothelium. The cellular distribution and reproductive state dependency of these three regulatory molecules varied. For all of them, however, ampullary segments contained more than isthmus; proliferative phase and/or postpartum specimens contained more than secretory phase; and postmenopausal specimens contained the lowest amounts. The cell periphery and nuclear/perinuclear area of the cells contained EGF, TGF-alpha, and their receptors. Immunogold electron microscopy showed the receptors to be present in cell membranes, cilia, basal bodies which control ciliary activity, endoplasmic reticulum, nuclear membranes, and chromatin. In summary, human fallopian tubes contain EGF, EGF/TGF-alpha receptor mRNA and protein, and TGF-alpha protein. The expression of all these regulatory molecules was dependent on anatomical region, cell type, and reproductive state of the fallopian tubes. These findings suggest that EGF and TGF-alpha may regulate numerous tubal functions, thus potentially influencing fertility in women.