Prognosis of colonic carcinoma is poor. The two most important factors having the greatest effect on survival are pathologic stage of disease and histologic grade of the tumor. Our study points towards the value of HLA-DR antigen in the prognosis of colonic carcinoma. We studied 31 cases of normal colonic mucosa, 12 cases of tubulo-villous adenoma, and 39 cases of invasive carcinoma for the detection of HLA-DR monoclonal antigen. Yet, we investigated the association of HLA-DR and DQ genes and adenoma and carcinoma by PCR. We also studied the T helper (TH) marker (CD4) in the lamina propria of the relevant cases, given that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. HLA-DR was expressed in 20 of 31 normal colonic mucosa (64.5%), 4 of 12 adenomas (33.3%), and in 10 of 39 invasive carcinomas (25.6%). No significant correlation between HLA-DR and DQ genes and adenoma or cancer of the colon was found. CD4 was expressed in 9 of 31 normal colonic mucosa (29%), 5 of 12 adenomas (42%), and in 26 of 39 invasive carcinomas (67%). The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. HLA-DR and DQ genes do not contribute to a susceptibility to adenoma or carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the colonic carcinoma.