inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. our purpose was to study the involvement of p53, apc, dcc, and rb genes in gastric carcinoma. method: loss of heterozygosity of the p53, apc, dcc and rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35s-datp, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone. results and discussion: no loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the rb gene in 23% (3/13) of the cases of intestinal-type gastric carcinoma. eighteen (81.8%) cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. the presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%). normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. the correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (p = .90). there was no correlation of gene alterations with the disease severity. conclusions: the inactivation of rb and p53 genes is involved in gastric carcinogenesis in our environment. loss of the rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with helicobacter pylori infection. the p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.