OBJECTIVES: Cancer of the pancreas is highly fatal and, despite extensive scrutiny, only cigarette smoking stands out as a likely causal agent in epidemiological studies. To explore to what extent different lifestyle factors are associated with the risk of pancreatic cancer, data from a large health screening survey in a county in Norway were analyzed. METHODS: Our study included 31,000 men and 32,374 women initially free from any diagnosed cancer, and during 12 years of follow-up, 166 incident cases of pancreatic cancer were diagnosed at the Cancer Registry. RESULTS: Compared with never smokers, we found a two-fold increased risk among current smokers, and a dose-response association with number of cigarettes (p for trend = 0.02 for both men and women) and with number of pack-years (p for trend = 0.02 for men and 0.01 for women). The risk among former smokers quitting more than 5 years before study entry was close to the risk of never smokers. Compared with persons who reported never or infrequently to be physically worn out after a day's work, the relative risk (RR) among those who nearly always became worn out was 2.9 (95% confidence interval (CI) = 1.4-5.8) for men and 3.8 (95% CI = 1.6-9.2) for women. Divorced or separated men had a risk of 3.1 (95% CI = 1.3-7.2) compared with married men. We observed a higher risk among women in occupations of high socioeconomic status (RR = 2.5; 95% CI = 1.2-5.2), and among men occupied in farming, agriculture or forestry (RR = 2.1; 95% CI = 1.1-4.0), compared with persons in occupations of low socioeconomic status. CONCLUSIONS: Our results confirm the findings of previous studies that indicate a causal role of cigarette smoking in pancreatic cancer. Moreover, we found that the risk of former smokers may approach the risk of never smokers within a few years subsequent to quitting.