The antibody response of patients was used to characterize the autoantigens in human colorectal carcinoma. Twenty-seven primary and 13 metastatic carcinomas with paired normal tissues were extracted and transferred onto nitrocellulose membranes by the Western transfer technique. After the transfers were incubated with the serum of the patient from whom the tumor was derived, autoantigens were identified by indirect immunoperoxidase staining. All tumors contained at least one autoantigen. Six tumor-associated autoantigens, ranging in molecular weight from 26 to 58 kilodaltons (kD), were identified by antibodies in 25% or more of the sera. Eleven metastases expressed a 41-kD autoantigen that was present in only a third of the extracts of normal liver or lung. Thus, the number of dominant polypeptide autoantigens in colorectal carcinoma is restricted to six molecules. These autoantigens may be organ-associated antigens that are expressed by neoplastic cells. The 41-kD autoantigen may be a potential marker for metastases. A generic vaccine appears to be feasible for colorectal carcinoma since the number of dominant antigens is limited.