We tested whether asthma diagnosis is associated with weight gain and physical activity in 4,547 18 to 30-yr-old African American and white men and women, followed prospectively for up to 10 yr. Baseline asthma was most frequent in African American men. Incident asthma was more frequent in women. Incident asthma was associated with highest and lowest baseline and change in body mass index (BMI), in a J-shaped curve, after adjustment for other factors. When stratified by sex, this association was seen only in females. Subjects on average decreased physical activity and gained weight over time, but there was no significant difference in asthma prevalence by physical activity at baseline or asthma incidence by change in physical activity. Cigarette smoking in females was significantly associated with asthma incidence, but serum cotinine level at baseline among nonsmokers (reflecting environmental tobacco smoke [ETS] exposure) was not significantly associated with asthma. We conclude that gain in BMI predisposes to new asthma diagnosis in female young adults, but decreased physical activity does not explain the association of weight gain with asthma.