The expression of various epitopes of epidermal growth factor receptor (EGFr) and mutational activations of ras gene product p21 in colorectal primary cancers from 16 patients have been analyzed in this study. Eight noncancerous colons were used as controls. Indirect immunoperoxidase staining was performed using Avidin-Biotin Complex assay. Monoclonal antibodies against carbohydrate and polypeptide epitopes of EGFr and monoclonal antibodies against "wild-type" and "mutant" ras p21 were used as specific probes. There was no specific expression of the polypeptide epitope of EGFr observed in any of the colon cancers or normal colon tissues. Four of the sixteen tumors (25%) expressed the carbohydrate epitope of EGFr. Glycine----arginine mutation and glycine----valine mutation of codon 12 in ras p21 was observed in 40 and 31% of colon cancers, respectively. Although normal colon showed expression of wild-type ras in about half the cases studied, there was no mutational activation of the ras genes. The morphologically adjacent normal colon mucosa in cancer patients expressed varying levels of mutational activation involving the codon 12. The presence of unusual carbohydrates relating to the EGFr and the products of ras gene activation by point mutations in colon cancers may imply a functional role in transformation.