The extensive pulmonary vasculature results in the lungs being intimately exposed to circulating blood. As increased serum osmolality may be associated with an increase in pro-inflammatory activity, this has the potential to result in damage to the lungs and reduced lung function. The objective of the present study was to test the hypothesis that increased serum osmolality is associated with a lower forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The present study was a cross-sectional study of 10,602 participants in the Third National Health and Nutrition Examination Survey aged > or = 17 yrs for whom there were adequate data on all outcomes and exposures. After adjustment for age, smoking and other confounding factors, increased serum osmolality was inversely associated with both FEV(1) and FVC. An increase of 1 sd in serum osmolality was associated with a decrease in both FEV(1) of 19.8 mL and FVC of 35.3 mL. The constituent assays demonstrated a complex relationship with both FEV(1) and FVC. Increased serum osmolality was associated with decreased forced expiratory volume in one second and forced vital capacity. If causal, this may have implications for the understanding of the processes that are involved in the pathophysiology of decline in lung function.