Objective: Obesity risk is negatively associated with physical activity and positively associated with time spent in sedentary behaviors. Yet, it is not known how different combinations of sedentary and active behavior are associated with body mass index (BMI). This study examined the interaction between time spent in physical activity and sedentary behavior on BMI in US adults. Design: Cross-sectional, data from the 2006 American Time Use Survey. Subjects: 10 984 non-underweight adults (aged 21 þ years). Measurement: A phone interview assessed all activities performed in the past 24 h, height, weight, health status, and other sociodemographic characteristics. Time spent in (1) moderate-to-vigorous leisure-time physical activity (MVPA), (2) active transportation (walking, biking), (3) sedentary leisure activities (TV/movie watching, computer use, playing games, reading), and (4) sedentary transportation (motorized vehicles) was determined from activity coding. BMI was calculated. Results: After adjusting for age, gender, education level, race/ethnicity, and health status, sample-weighted linear regressions found significant interactions for leisure MVPA  TV/movies, leisure MVPA  playing games, active transportation  sedentary transportation, and active transportation  reading (Pso0.0001). For example, the group of adults watching o60 min per day of TV/movies and engaging in X60 min per day of leisure MVPA had lower average BMI compared to the group watching o60 min per day of TV/movies and reporting o60 min per day of leisure MVPA (Po0.0001). In contrast, for adults watching X189 min per day of TV/movies, there was not a significant difference in BMI by time spent in leisure MVPA. Conclusion: Data from a US time use survey indicate that the strength of the association between certain types of sedentary behavior and BMI varies according to time spent in certain types of physical activity and vice versa.