It has been reported that HLA-DR is a potent inducer of thrombin generation. Human colorectal cells (GEO, WiDr, DLD-1, and MIP) that lack the constitutive expression of HLA-DR cause platelet aggregation through a thrombin-dependent mechanism. Treatment with recombinant human gamma-interferon induced the expression of HLA-DR in the GEO, WiDr, and DLD-1 cells, whereas the MIP cell line remained HLA-DR negative. The concurrent analysis of tumor cell/platelet interaction after gamma-interferon treatment showed a decrease in platelet proaggregating activity of either the responsive GEO (highly expressing HLA-DR) or the unresponsive MIP (HLA-DR negative) cells. Furthermore, the DLD-1 (moderately expressing HLA-DR) cells showed an increase of proaggregating activity after gamma-interferon treatment, whereas WiDr (highly expressing HLA-DR) cells did not modify their activity. These results suggest a lack of a role of HLA-DR in the in vitro platelet proaggregating activity of human colorectal tumor cells.