This study was conducted to investigate the p53 gene alterations in 25 surgically-resected gastric adenocarcinomas in the Korea Cancer Center Hospital by polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) for exons 4-8 and immunohistochemical staining (IHCS) with anti-p53 antibody, DO-7. p53 mutations were detected in nine (36%) out of 25 cancer tissues by PCR-SSCP in exon 4-8: 0,1,1,6 and 1 mutations in exons 4,5,6,7 and 8, respectively. All tissues were also tested by IHCS, and positive staining was observed in 11 cases (44%). A discrepancy of the results between the two methods was observed in four cases. In one which showed positivity by PCR-SSCP a negative reaction by IHCS, the two base deletion was observed in exon 7. On the other hand, in three cases the mutation was detected only in IHCS but not in PCR-SSCP. The exact mechanism by which this discrepancy develops is not clear at present, although it may be due to the mutation of other exons not tested in this study or the relatively low sensitivity of the PCR-SSCP method. The incidence of p53 gene mutations was analysed according to pathologic stage and histological differentiation, but no significant difference was observed between the p53 alterations and these factors. By combined use of PCR-SSCP and IHCS, 48% of the 25 primary gastric cancer were considered to have mutations of the p53 gene. These results suggest that p53 mutation is not an infrequent event in primary gastric cancer and the p53 gene plays an important role in the carcinogenesis process of gastric cancer.