Measures of obesity, especially central adiposity, have been associated with reduced lung function. However, previous studies may have been affected by confounding by physical activity and fitness. This study aimed to examine the relationship among body fatness, fat distribution, and lung function, adjusted for physical activity energy expenditure (PAEE) and aerobic fitness (VO(2)max), in a cohort of British white adults with a family history of type 2 diabetes. A total of 320 adults (mean age 40.4 +/- 6.0 years) attended for anthropometric and VO(2)max testing, and had ambulatory heart rate monitoring for 4 days to determine PAEE. Spirometry was used to measure forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC). The tests were repeated 12 months later, and a cross-sectional analysis using linear regression with repeated measures was performed. Measures of obesity (BMI, waist circumference (WC), fat mass (FM), body fat percentage (BF%)) were associated with lower lung function in men and women (P < 0.01), while waist-to-hip ratio (WHR) was associated with lower lung function in men only (P < 0.001). Associations remained after adjusting for age, smoking status, height, PAEE, and VO(2)max. The estimated difference in mean FEV(1) and FVC per unit increase in the exposure measures were consistently stronger in men compared to women (P for interaction <0.001). Obesity is inversely associated with lung function in adults, but central fat distribution appears to have a stronger relationship with respiratory mechanics in men than in women. These associations were independent of the degree of physical activity and aerobic fitness in this cohort.