Activation of the cellular oncogene ras has been implicated in many types of human malignancies. In this study, the relative levels of p21 protein product of ras (p21ras) in primary and metastatic colon tumors were compared to those in adjacent normal tissues. Nine of the 17 primary tumors had substantially elevated levels of p21ras with respect to adjacent normal tissues. Eight of these tumors were from Dukes' B and C stages. Four of the five tumors classified as "D" stage (in which distant metastases are present) did not show elevated levels of p21ras. In metastases from primary colon tumors, nine of nine were considerably reduced in p21ras expression regardless of the site of metastasis. These data suggest that elevation of p21ras may be a common event in early stages of colon tumors, and tumor progression may lead to a more autonomous population of cells in which other growth factors supplant the role of this protein.