Background: Systemic inflammation has been associated with reduced lung function. Adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and P-selectin, figure importantly in initiating the inflammatory response. We studied the association between ICAM-1 and P-selectin concentrations and lung function in the Coronary Artery Risk Development in Young Adults study. Methods: Spirometry testing was conducted at years 5, 10, and 20. ICAM-1 and P-selectin were assayed at year 15. Results: Complete data were obtained from 2,455 participants. We first predicted year-20 lung function from year-15 ICAM-1 concentration data. After controlling for race, gender, height, age, physical activity, smoking status, alcohol intake, BMI, and asthma status, all taken at year 15, the year-20 FVC was 164 mL higher (p < 0.0001) and FEV1 was 115 mL higher (p = 0.0003) in the lowest ICAM-1 concentration quartile than the highest ICAM-1 quartile, whereas the FEV1/FVC ratio showed no association (p = 0.25). We then predicted the year-15 ICAM-1 concentration from year-5 lung function and change in lung function (year 10 - year 5). The year-15 ICAM-1 concentration was about 13 ng/mL higher in the lowest vs highest quartile of either the year-5 FVC (p = 0.01) or year-5 FEV1 (p = 0.005). Year-15 ICAM-1 concentration was unrelated to year-5 FEV1/FVC ratio. Greater loss in FVC and FEV1 (year 10 - year 5) also was associated with higher year-15 ICAM-1 concentrations. Associations between P-selectin and lung function followed a similar but weaker pattern to that observed for ICAM-1. Conclusions: These data suggest a bidirectional association between circulating adhesion molecules, such as ICAM-1 and P-selectin, and pattern of lung function change in adults.