As part of the SEARCH Collaborating Study Group of the International Agency for Research on Cancer (IARC), a population-based case-control study of cancer of the pancreas was conducted in Montreal, interviewing 179 patients and 179 controls matched for age, sex, and language (French) and selected by a modified random-digit dialing method. Results showed a positive and strong association between cigaret smoking and pancreatic cancer. Total fat, particularly saturated fat, and cholesterol consumption and excess energy derived from fat were associated with positive risk; dietary fiber intake, retinol equivalent, beta-carotene, vitamin C, and calcium showed inverse association with risk. History of such medical conditions as constipation, gallbladder problems, and diabetes was also found to be associated with risk. More important, 7.8% of the pancreatic cancer patients reported a positive family history of the same disease, as compared with 0.6% among controls, a 13-fold difference between cases and controls. Within the original case-control study a further study of patients with instances of familial pancreatic cancer was conducted, based on 14 cases and 56 matched controls. The results support the finding of the main study, and there were no apparent differences in environmental-risk-factor profile in familial and nonfamilial cases. This unusual aggregation of familial pancreatic cancer among French Canadians cannot be explained by environmental factors alone. Some familial predisposition (hereditary factors) may play an important role in the etiology of this cancer, at least in this study region. The findings suggest the potential importance of conducting genetic studies of pancreatic cancer.