The expression of HLA-A,B,C antigens and lymphocyte function-associated antigen 3 in human colorectal adenomas and adenocarcinomas was studied by immunohistochemistry. None of 10 adenomas and only 1 of 30 carcinomas had lost expression of all HLA-A,B,C molecules. On the other hand, focal loss of an HLA-B product was seen in 2 of the adenomas, and complete losses of tumor cell HLA-A2 (in 7 of 13 cases), HLA-Bw4 (in 4 of 13 cases), and HLA-A3 (in 1 of 6 cases) were seen in the carcinomas. No complete losses of HLA-A1 (in 6 cases) or HLA-Bw6 (in 22 cases) occurred in the carcinomas. In addition, 1 of 20 adenocarcinomas totally lacked lymphocyte function-associated antigen 3. Because a loss of tumor cell HLA-A,B,C antigen or lymphocyte function-associated antigen 3 could be selected for through an advantage in escape from cytotoxic T-lymphocyte attack, our results suggest that immunoselection may be a more important mechanism in tumor progression than has previously been assumed.