The expression of tumor necrosis factor alpha and its mRNA was investigated in surgical biopsies from idiopathic pulmonary fibrosis by immunohistochemistry, in situ hybridization, and Northern blotting. Normal areas of lungs resected for cancer were used as controls. Tumor necrosis factor alpha mRNA levels were higher in idiopathic pulmonary fibrosis than in normal lungs as determined by Northern blots. In normal lungs, tumor necrosis factor alpha and its mRNA were identified in alveolar and interstitial macrophages. In fibrotic lungs, tumor necrosis factor alpha was detected in macrophages and, to a greater extent, in epithelial cells (presumably type II cells) lining the thickened septae. Tumor necrosis factor alpha mRNA was found only in some interstitial cells and some of the cells lining the alveolar septae. An elevated concentration of tumor necrosis factor = alpha, particularly within the alveolar epithelium, might contribute to the alveolar damage and proliferation of interstitial cells in idiopathic pulmonary fibrosis.