We examined for germ-line p53 mutations and microsatellite instability in three gastric cancer patients who had family histories of gastric cancer aggregation. Although no germ-line p53 mutation was detected in these three cases, the replication error (RER) phenotype was observed in two of them. One base deletion in the sequence of ten repeating adenines of the type II transforming growth factor-beta receptor gene was detected in one of these two cases. Furthermore, there were young patients of 50 years and downward in their families. Therefore, it is possible that inherited disorders in mismatch repair systems contribute to high susceptibility to gastric cancers in these families.