Monoclonal antibody 17.13., derived from a fusion of splenocytes of a BALB/c mouse immunized with a surgically resected poorly differentiated human laryngeal recurrent squamous cell carcinoma (SCC) with mouse Sp2/0 cells, is an IgM-K which recognizes a cytoplasmic component of basal cells. Tissue sections of malignant and normal squamous epithelium, tumors of nonsquamous origin, and normal and malignant cytological specimens were tested with an immunoperoxidase assay. Seventy-nine of 81 (98%) SCC of the head and neck, 26 of 26 (100%) SCC of the cervical and female gynecological tract, 29 of 30 (97%) SCC of the lung, 19 of 19 (100%) SCC of the oral cavity, and 17 of 17 (100%) SCC-involved neck lymph nodes reacted strongly. Various carcinomas from breast, colon, ovary, and others were unreactive. In normal squamous epithelial tissues, monoclonal antibody 17.13. reacts only with basal cells but not the cells above the basal layers. Normal tissues from heart, liver, spleen, kidney, bladder, colon, ovary, stomach, pancreas, breast, lung, prostate, thyroid, and lymph nodes were unreactive with the exception of myoepithelial cells. Monoclonal antibody 17.13. may be useful in the diagnosis and management of SCC.