The loss of heterozygosity (LOH) at the bcl-2 gene locus and the expression of the bcl-2 gene were examined in gastric and colorectal carcinoma cell lines and carcinoma tissues. LOH at the bcl-2 locus was detected in 24% (4/17) of gastric and 60% (6/10) of colonic carcinomas, all of which were well differentiated adenocarcinomas, whereas LOH was not seen in poorly differentiated ones. On the other hand, 24% (5/21) of poorly differentiated stomach cancers overexpressed bcl-2 gene, whereas no overexpression was detected in well differentiated stomach cancer. Three gastric and three colorectal carcinoma cell lines, all of which were derived from poorly differentiated adenocarcinomas, expressed considerable levels of bcl-2 mRNA and protein. These results suggest that LOH at the bcl-2 locus is frequently associated with well differentiated adenocarcinomas of the stomach and colon, and bcl-2 overexpression has implications for the development of poorly differentiated adenocarcinomas of the gastrointestinal tract.