A marked influx of inflammatory cells occurs into the airways of patients with cystic fibrosis (CF), which may contribute to the development of lung injury. Leukocyte–endothelial adhesion molecules play a crucial role in the recruitment of inflammatory cells, and soluble forms of these molecules have been shown to increase in several inflammatory diseases. By using a capture ELISA, we determined serum levels of soluble ICAM-1 (sICAM-1), E-selectin (sE-selectin), and VCAM-1 (sVCAM-1) in patients with CF, in stable clinical conditions (n = 29, mean age: 25.8 ± 1.5 yr), and healthy control subjects (n = 12, mean age: 27.6 ± 1.5 yr). Clinical, spirometric, microbiological, and hematological assessments were made in all subjects. sICAM-1 and sE-selectin concentrations, but not sVCAM-1 levels were significantly increased in CF patients as compared with normal subjects (both p < 0.001). sICAM-1 levels were inversely related to FEV1 values (r = - 0.519, p = 0.004) and Schwachman score (r = - 0.405, p = 0.03) in CF patients. In 7 of 29 CF patients, soluble adhesion molecule levels were determined not only at the time of stable clinical conditions, but also before and after antibiotic treatment for a pulmonary exacerbation. sICAM-1 and sE-selectin levels increased in all patients at the time of the exacerbation, compared with levels at the time of stable conditions (p < 0.02 for both comparisons); antibiotic treatment induced a significant decrease of both circulating adhesion molecules (p < 0.02). The elevated serum levels of sICAM-1 and sE-selectin in CF patients, even when they are clinically stable, may reflect the marked and persistent inflammatory process in the disease.