Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with Crohn's disease (CD). In the latter condition p-ANCA were equally present in subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA were higher in patients with UC compared to CD patients, in particular when comparing patients with active disease. In contrast to findings in CD, patients with active UC had higher titers of p-ANCA than patients with inactive UC. Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA could not be identified in most of the cases. We conclude that, within the spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific for UC. When titers of p-ANCA are taken into account, the presence of high-titered p-ANCA, however, suggests active UC.