To assess the association between specific types of human leukocyte antigen and the risk of Epstein-Barr virus (EBV)-associated gastric carcinoma, serological typing for major histocompatibility complex class I and class II antigens was performed for 110 EBV-positive and 155 EBV-negative gastric carcinoma cases. In class I analysis, the frequency of B59 in the EBV-positive cases was higher than for the EBV-negative cases (odds ratio (OR) 3.06; 95% confidence interval (CI) 1.02-9.23). For class II antigens, DQ3 and DR9 frequencies in the EBV-positive cases were higher (OR 1.94; 95% CI 1.16-3.24 and OR 1.93; 95% CI 1.11-3.37, respectively), whereas DR11 frequency was lower than found in the EBV-negative cases (OR 0.10; 95% CI 0.01-0.79). After adjusting for multiple comparisons, only DR11 frequency remained significantly lower in the EBV-positive cases (P = 0.04), and the association of DQ3 was marginally significant (P = 0.05). These results suggest that the presence of DR11-restricted cytotoxic T cells (CTLs) related to EBV-associated gastric carcinoma, or a deficiency of DR11 and a high frequency of DQ3 may be genetic markers for a population at greater risk of EBV-associated gastric carcinoma. However, further extensive studies to more cases and DNA typing are needed because our findings in this study are exploratory.