Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-α (TGFα), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of themdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGFα staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGFα, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein.