A community-based case-control study was carried out to assess multiple risk factors and familial aggregation of nasopharyngeal carcinoma (NPC). All of the 347 pathologically-confirmed NPC new cases were serially recruited from the National Taiwan University Hospital, and healthy community controls one-to-one matched with cases on age, sex and residence were selected from household registration offices. NPC risk factors were obtained from the study subjects through standardized interviews according to a structured questionnaire. Levels of antibody to EBV-specific DNase (anti-EBV DNase) and IgA antibody to EBV viral capsid antigen (anti-EBV VCA) were determined by standard methods blindly. Multiple logistic regression analysis for matched data showed significant associations of NPC with high levels of anti-EBV DNase and anti-EBV VCA independently. The effect of cigarette smoking on NPC was modified by age. The older the age, the more striking the dose-response relation between cigarette smoking and NPC. There was no significant association between alcohol consumption and NPC. Malarial infection history was associated with NPC with an odds ratio of 2.2, but the association was significant in males only. First-degree relatives of NPC cases had a greater NPC-affected rate than those of matched healthy controls with a relative risk of 19.2, and the heritability of NPC was estimated as 0.60 (95% confidence interval = 0.55-0.64) based on the multifactorial inheritance model. Familial NPC cases were younger than sporadic cases, but environmental risk factors were similar in the two groups.