The nature and frequency of pulmonary involvement in systemic lupus erythematosus (SLE) is controversial. We reviewed the clinical and pathologic features of 120 patients with SLE described in autopsy records at The Johns Hopkins Hospital to determine the pulmonary parenchymal changes that could be attributed directly to SLE. Each case was reviewed to determine the extent of extrapulmonic SLE and possible alternative explanations for the observed lung pathology. Moderate or severe pulmonary parenchymal alterations that were attributed to SLE were found in 22 patients (18 percent). Five patients with interstitial fibrosis, two with pulmonary vasculitis, and one with pulmonary hematoxylin bodies were attributable only to SLE, as were 11 of 15 (73 percent) patients with interstitial pneumonitis. Alternative explanations for findings previously attributed to SLE included congestive heart failure, renal failure, infection, aspiration, oxygen toxicity and increased intracranial pressure. Alveolar hemorrhage, thought to be a feature of acute lupus pneumonitis, was unexplained in only two of 29 (7 percent) patients, alveolar wall necrosis was unexplained in one of seven (14 percent) and edema was unexplained in three of 70 (4 percent). Hyaline membranes, present in four patients, were always explained. Pleuritis and pleural effusions were attributed to SLE in 22 of 36 (61 percent) and three of 28 (11 percent) patients, respectively. The findings suggest that many nonspecific pulmonary lesions previously attributed to SLE, such as alveolar hemorrhage, alveolar wall necrosis, edema and hyaline membranes, are probably secondary to intercurrent infection, congestive heart failure, renal failure or oxygen toxicity.