&NA;To gain a better understanding of the biologic development of rectal adenicarcinomas, the authors evaluated the level ofrasgene protein product (p21) in the available material of 74 Dukes'B adenocarcinomas, 64 Dukes' C adenocarcinomas, and 60 lymph‐node metastases resected at the University of Chicago Medical Center between 1965 and 1981. Pathologic slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis and measurement of p21 content. P21 titers were obtained using the RAP‐5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution giving definitive staining using the avidinbiotin peroxidase method. The analysis indicated that a higher percentage of Dukes' stage C rectal adenocarcinomas had high (≥1:40,000) p21 titers than Dukes' B adenocarcinomas (68.8vs.51.4 percent, respectively,P<0.05). In view of recent data suggesting thatrasoncogene expression confers invasive and metastatic capabilities to NIH 3T3 cells, the authors believe this study offers evidence that overexpression ofrasoncogene with overproduction of p21 protein product may be an important prerequisite for the acquisition of metastatic capabilities in the early stages of colon cancer.