The acute lung injury of adult respiratory distress syndrome (ARDS) is characterised by inflammatory cell accumulation and activation in the lung. Selectins are a family of adhesion molecules implicated in leucocyte-endothelial adhesion, whose receptors can exist in a cleaved, soluble form. We investigated whether circulating soluble selectin adhesion molecules, obtained from ARDS at-risk patients, were associated with subsequent ARDS development. 82 patients, at risk of ARDS, were enrolled from three well-defined groups (multiple trauma, pancreatitis, perforated bowel). Plasma samples were obtained on hospital presentation and soluble L, E, and P, selectins were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA). 14 patients subsequently developed ARDS. Initial plasma soluble L-selectin (sL-selectin) levels were significantly lower in patients who progressed to ARDS compared to those who did not (p = 0.0001; 95% Cl for mean in ARDS patients as percent of that in non-ARDS patients, 27-61%). Moreover concentrations were lower than in 62 normal volunteers (range 0.37-6.55, median 1.83 micrograms/mL, n = 62), suggesting that a selective reduction of sL-selectin correlates with susceptibility. In addition, a significant correlation was found between low values of sL-selectin and indices of subsequent lung injury including requirement for ventilation (p = 0.0001) and degree of respiratory failure (p = 0.0001). A significant correlation was also found between low values of sL-selectin and patient mortality (p = 0.002). These results elucidate the inflammatory cell endothelial interactions in the early stages of ARDS and may be of prognostic value.