Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disorder restricted to the lungs. Leukocyte entry into the area of inflammation is regulated, at least partly, by endothelial expression of leukocyte-selective cell adhesion molecules (CAMs). To investigate the relevance of these CAMs to the accumulation of leukocytes in IPF, we examined the expression of E-selectin (endothelial leukocyte adhesion molecule-1; ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by immunohistochemistry in lung tissue from nine patients with IPF and five nonsmoking normal subjects. The results demonstrated that in normal lungs, ICAM-1 was weakly expressed on endothelial cells, but neither E-selectin nor VCAM-1 was detected. In the lungs of patients with IPF, E-selectin expression on endothelial cells was restricted to honeycombing regions. Endothelial expression of ICAM-1 was increased throughout the tissue, but VCAM-1 was not detected in IPF. The distribution of leukocytes in lungs with IPF consisted of mostly lymphocyte accumulation in the interstitium and neutrophil accumulation within the airspaces of honeycomb regions. These results suggest that E-selectin may play a role in the recruitment of neutrophils in regions of honeycombing and that ICAM-1 may play a role in lymphocyte recruitment into the interstitium in addition to contributing to neutrophil recruitment in regions of honeycombing in patients with IPF.