Pulmonary hemorrhage is a rare and often fatal complication of systemic lupus erythematosus (SLE). Treatment with high-dose steroids and cyclophosphamide has been of only modest value, with a reported mortality of up to 92%. We have recently seen three patients with active SLE who developed acute life-threatening pulmonary hemorrhage. Diagnostic evaluation of these patients showed negative sputum and blood cultures, negative glomerular basement membrane antibodies, and negative antineutrophilic cytoplasmic antibodies. In two patients, an open-lung biopsy was performed, and histological examination showed granular alveolar immunofluorescence staining for immunoglobulin and complement components. Treatment with plasmapheresis was initiated with prompt resolution of symptoms and clearing of chest radiograph. Two patients had recurrent bleeds despite treatment with cyclophosphamide and high-dose steroids and required repeated intubation. Plasmapheresis resulted in rapid radiographic and clinical improvement on each occasion. Two patients survived long-term and are presently without pulmonary problems; one patient died of sepsis after initial response to plasmapheresis. The dramatic improvement of the pulmonary disease in these patients leads us to conclude that rapid initiation of plasmapheresis should be strongly considered in SLE patients with severe, life-threatening pulmonary hemorrhage.