Obesity and lack of physical activity have been inconsistently associated with pancreatic cancer. Using data from a self-administered baseline questionnaire (1995-1996), the authors investigated the association between adiposity and physical activity and pancreatic cancer in 495,035 participants of the National Institutes of Health-AARP Diet and Health Study who were aged 50-71 years. To avoid the influence of subclinical disease, follow-up time started 1 year after baseline, and subjects with a body mass index (BMI) of <18.5 kg/m(2) were excluded. A subcohort (n = 302,060) completed a second questionnaire with information about physical activity and waist and hip circumference. During follow-up though 2000, 654 pancreatic cancer cases were identified. The authors used Cox proportional hazard models to generate adjusted hazard ratios and 95% confidence intervals. Compared with those with a BMI of 18.5-<25, those with a BMI of >/=35 had a 45% greater pancreatic cancer risk (95% confidence interval (CI): 1.04, 2.02; p(trend) = 0.02). Significant positive associations for BMI were observed among nonsmokers (for BMI > or =35: hazard ratio = 1.70, 95% CI: 1.14, 2.53; p(trend) = 0.004) but not recent smokers (p(interaction) = 0.08). Waist circumference was positively associated with pancreatic cancer (fourth vs. first quartile: hazard ratio = 2.53, 95% CI: 1.13, 5.65; p(trend) = 0.04) in women but not men. The authors observed no association with physical activity. Their results suggest a positive association between adiposity and pancreatic cancer.