Lack of energy balance, or greater energy intake than expenditure as indicated by a large body mass index (BMI), has been associated with colon cancer, although less is known about its association with rectal cancer. In this study, we examined the association between BMI, energy intake, and energy expenditure and their combined effect on rectal cancer risk. A population-based case-control study was conducted in Utah and Northern California. Incident cases (n = 952) of rectal cancer and population-based controls (n = 1205) were interviewed between 1997 and 2002 to obtain detailed information on body size, dietary intake, and physical activity patterns. BMI (kg/m(2)) was not associated with rectal cancer in either men or women. Participation in vigorous leisure-time physical activity over the past 20 yr was associated with a significant 40% reduction in rectal cancer risk. Energy intake was associated significantly with increased risk of rectal cancer, especially among people whose diagnosis was prior to age 60 yr (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.7-9.1 for men; OR = 2.8; 95% CI = 1.1-7.2 for women). There was a significant interaction between energy intake and energy expenditure, although not between BMI and either energy intake or energy expenditure. These data suggest that large BMI, an indicator of lack of energy balance, is not an important component of the etiology of rectal cancer. However, both physical activity and energy intake were significantly associated with rectal cancer risk. These data suggest that energy expenditure and energy intake alter rectal cancer risk through mechanisms other than energy balance.