Extrahepatic bile duct (EBD) cancers are rare and their risk factors are poorly understood. Except for a history of gallbladder diseases, evidence for other potential risk factors, such as excess body weight and use of tobacco and alcohol, is scant. A case-control study was conducted to examine risk factors for EBD cancers, including ampulla of Vater tumors, among Los Angeles County (California, USA) residents. Included were 105 histologically confirmed cases diagnosed between 1 March 1985 and 31 October 1989, aged 30 to 84 years, and 255 population-based controls frequency-matched to cases by gender and age in five-year groups. Cases and controls were interviewed about their demographic background and potential risk factors, including tobacco, alcohol, and beverage consumption, diet, medical history, and reproductive factors among women. For deceased cases, their next-of-kin were interviewed. Risk of cancers of both subsites of extrahepatic duct and ampulla of Vater increased with smoking of cigars/pipes or cigarettes. For both men and women, risks increased twofold or more among those who smoked cigarettes for 50 or more pack-years. While a history of gallbladder diseases substantially increased the risk of cancers of both subsites, excess body mass index was associated only with cancer of extrahepatic duct subsite (odds ratio [OR] = 4.0, 95 percent confidence interval [CI] = 1.1-14.2 among men and OR = 2.7; CI = 0.8-9.4 among women in the highest quartile relative to those in the lowest quartile). Alcohol drinkers had lower risks compared with nondrinkers, but no consistent trend was observed with amount consumed.(ABSTRACT TRUNCATED AT 250 WORDS)