Tumor-specific antisera against dehistonized chromatin isolated from transplantable colon adenocarcinoma (from male noninbred Sprague-Dawley rats) were produced. The specificities of these antisera were determined by complement fixation. In the presence of these antisera, only chromatin from colon adenocarcinoma significantly fixed complement, whereas chromatins isolated from normal rat colon epithelia were inactive. Administration of 1,2-dimethylhydrazine to rats produced an early change in the immunospecificity of colon epithelial chromatin similar to that for colon adenocarcinoma. Several lines of experimental evidence indicated that nuclear antigen was not a carcinoembryonic antigen-like substance. Common antigens were also present in human colon adenocarcinomas.