p68 is an interferon-inducible protein kinase which is a key factor in the regulation of both viral and cellular protein synthesis. Since p68 plays a central role in cellular protein synthesis, we hypothesized that it would parallel translational activity, and thereby correlate with cellular differentiation in both normal and neoplastic cell types. Using the anti-p68 monoclonal antibody, TJ4C4, we have previously noted a correlation of p68 expression with the degree of cellular differentiation in the human upper aerodigestive tract and lung. During normal human fetal development, p68 is abundantly expressed in the upper aerodigestive tract and lungs, but considerably less so in the colon. In order to determine if this fetal expression pattern correlated with the pattern seen in adult colon and colonic adenocarcinomas, we analyzed the expression pattern of p68 in 80 patients with adenocarcinoma of the colon. Using light microscopic evaluation of immunoperoxi-dase-stained tissue sections, a spectrum of p68 expression was noted among the tissue samples. Increased p68 levels were noted in the majority of tumors with increased cellular differentiation, and those tissues with decreased p68 were, in general, less differentiated. These data are consistent with the concept that the expression of p68 parallels the degree of cellular differentiation, and are consistent with previously reported studies using this antibody. The limited fetal expression pattern of p68 in the colon and the variable correlation of p68 with differentiation suggests that p68, as well as other translational regulators, can be important in assessing the biological potential of tumors arising in the colon.