A polyclonal antibody detecting S-100 protein (S-100) and a monoclonal antibody demonstrating epithelial cell (Lu-5) were used in addition to routine, hematoxylin-eosin stain to improve the identification of tumors of neural or epithelial origin diagnosed in conventionally treated tissue from rat bioassays. Among 108 lesions tested for S-100, 51 reacted positively; they included benign and malignant schwannoma, endomyocardial disease, some cases of benign and malignant thymoma, and renal tubular adenoma. S-100 protein is considered particularly useful for discriminating of neoplasms of Schwann cell origin from mesenchymal tumors. 31 of 51 lesions tested for Lu-5 reacted positively: they comprised adenoma, carcinoma, benign and malignant thymoma and atriocaval node tumor of the heart. Lu-5 was especially useful to distinguish epithelial from mesenchymal neoplasms and was capable of identifying epithelial elements in lymphocyte-rich thymomas as well as in dedifferentiated or autolytic tumors. The binding of both antibodies in neoplastic tissue was compared with a complete set of anatomically normal rat tissues.