Tumor-antigen 4. Its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus. The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot. 