HLA-A,B,C and HLA-DR molecules are involved in cognate LFA-3 (CD58) in antigen-independent T-cell/target-cell interaction. T-cell-mediated host-versus-tumor response might therefore depend on the presence of both types of molecules on the surface of the target cell. To investigate whether presence or absence of these molecules in colorectal carcinoma influences the recurrence rate, 149 patients who underwent curative surgery were surveyed for a maximum of 65 months (mean, 48 months). As determined by immunohistochemistry, aberrant reduction of HLA-A,B,C determinants was observed in 34.9 and a complete loss in 8.7% of the tumor specimens. An induction of HLA-DR molecules was found in 55.0 and of the HLA-DR-associated invariant chain (Ii) in 81.9%. An abnormal reduction of LFA-3 was detected in 43.6%, while a complete loss of this structure was observed in 6.7%. Reduction/loss of HLA-A,B,C was correlated with reduction/loss of LFA-3 (p = 0.03). In contrast to the prognostic role of tumor stage and grade, the presence vs. absence of all these structures was not correlated with the recurrence rate. We conclude that, although encoded on different chromosomes, an abnormal reduction/loss of HLA-A,B,C and LFA-3 might be the consequence of one transacting down-regulating signal. However, the resulting deviant immunophenotypes do not profoundly influence survival and growth potential of residual tumor cells.