The objective of this study was to determine the significance of the antineutrophil cytoplasmic autoantibodies (ANCAs) from the clinicopathologic viewpoint of pulmonary hemorrhage occurring as a prominent event of disease. Forty-three consecutive patients with both pulmonary hemorrhage as a prominent clinical manifestation and a positive test for antineutrophil cytoplasmic autoantibodies were studied. Thirty-six patients underwent open lung biopsy, including histologic, tissue immunofluorescence, and microbiologic studies. Immunoassays were performed to investigate the antigenic specificities of antineutrophil cytoplasmic autoantibodies in the patients studied. All patients with lung biopsy confirmation had pauci-immune hemorrhagic alveolar capillaritis as the main morphologic substrate. In addition, renal involvement in the form of pauci-immune crescentic glomerulonephritis was a common finding. Serum samples from the 43 study patients contained antibodies that were monospecific for proteinase 3 (n = 13) or myeloperoxidase (n = 30). In our study, whereas anti-proteinase 3 antibodies were mainly detected in patients with alveolar capillaritis and a well-established diagnosis of Wegener's granulomatosis, antimyeloperoxidase antibodies were principally found in those patients who had alveolar capillaritis and polyarteritis nodosa not only as a primary finding but also accompanying other diseases. However, a significant number of patients with alveolar capillaritis and antimyeloperoxidase antibodies showed no evidence of polyarteritis nodosa (idiopathic pulmonary-renal syndrome and isolated forms of pulmonary hemorrhage). We conclude that in patients presenting with pulmonary hemorrhage as a prominent event of disease, antineutrophil cytoplasmic autoantibodies are a new clue strongly supportive of a pulmonary capillary vasculitis, irrespective of the primary underlying disease. Moreover, the antigenic subtype of antineutrophil cytoplasmic autoantibodies helps in recognizing the type of vasculitic disorder involved.