Abnormalities affecting tumour suppressor genes on chromosome 5q21 are increasingly recognised as important in the pathogenesis of a variety of human cancers, particularly of the gastrointestinal tract. We have examined a series of gastric and pancreatic cancers from European patients for loss of heterozygosity (LOH) of markers within and around the APC and MCC genes on chromosome 5q21 using restriction fragment length polymorphism and polymerase chain reaction techniques. We find that LOH of the APC and MCC genes is particularly frequent in gastric cancers of diffuse type, but very infrequent in pancreatic cancers. We have also used single-strand conformational polymorphism to screen for abnormalities of the sequence of the APC and MCC genes in a panel of pancreatic cancer cell lines. Our results suggest that there are distinct differences in the molecular pathogenesis of gastric and pancreatic cancer and that abnormalities of APC and MCC may be involved particularly in the diffuse type of gastric cancer.