Previous studies showed that apoptotic epithelial cells were involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP); however, little is known about apoptosis in chronic hypersensitivity pneumonitis (HP). This study was performed to examine whether apoptosis has a role in chronic HP. We performed immunohistochemical studies for p53, p21, Fas, Fas ligand, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling methods on surgical lung specimens. The expression of Fas and Fas ligand was up-regulated in UIP-like lesions compared with nonspecific interstitial pneumonia (NSIP)-like lesions. The expression of p53 and p21 on epithelial cells increased significantly in UIP-like lesions compared with fibrotic NSIP-like lesions and in fibrotic NSIP-like lesions compared with normal lung tissues. These results confirm that apoptotic epithelial cells are present in chronic HP as seen in IPF. Augmented epithelial apoptosis may contribute much more to UIP-like lesions than to NSIP-like lesions in chronic HP.