To clarify the role of p53 in the development of Epstein-Barr virus (EBV)-associated gastric carcinoma, we examined DNA-ploidy pattern, the immunoreactivity of p53, p21(WAF1) and Ki-67 and the incidence of mitosis and apoptosis in EBV-positive and -negative gastric carcinomas of similar histology: a lace pattern and/or gastric carcinoma with lymphoid stroma. There was no significant difference in DNA-ploidy pattern, Ki-67 index or frequencies of mitosis and apoptosis between the two groups. In deeply invasive tumours (involving the muscularis propria or deeper), p53-positive ones were rare in the EBV-encoded small RNA (EBER)-positive group and very common in the EBER-negative group, while in superficial tumours, around one-half of them were p53-positive in both groups. In p53-positive superficial tumours, p21(WAF1)-positive ones accounted for 80% in the EBER-positive group and were scarce in the EBER-negative group. It is thus possible that p53 immunoreactivity reflects the overexpression of wild-type p53 and the stabilization of mutant p53 in the EBER-positive and -negative groups, respectively. The role of p53 in tumour development seems to be smaller in EBER-positive than in -negative gastric carcinomas.