P-glycoprotein (Pgp), encoded by the multidrug-resistance gene (MDR1), is an active efflux pump for many structurally diverse lipophilic compounds. Using peroxidase-antiperoxidase immunohistochemistry technique and four anti-Pgp monoclonal antibodies directed against different epitopes of the molecule, we examined the distribution of Pgp in normal human tissues and squamous cell carcinomas of the head and neck. All four antibodies detected Pgp in bronchial cells, mammary ductal epithelium, gallbladder epithelium, epithelia of small and large intestine, bile canaliculi, dermal sweat glands, proximal tubules of kidney, endometrium, trophoblasts, adrenal gland, and capillaries of central nervous system, testis, and papillary dermis. Of the 23 head and neck squamous cell carcinomas, about 60% had detectable Pgp. It is possible that differences noticed between antibodies are due to cross-reactivity to proteins unrelated to MDR1. Care must be taken in interpreting staining results when only one or two monoclonal antibodies are used.