pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high frequency in patients with ulcerative colitis. The purpose of this study was to investigate the frequency of pANCA in different mouse models of colitis and to determine whether there is any cross-reactivity of pANCA with bacterial antigens. Sera from 146 colitic mice and controls and from 30 patients with ulcerative colitis were tested for the presence of pANCA by indirect immunofluorescence with or without prior absorption with homogenized murine cecal bacteria. pANCA was found in 24 of 36 IL10-1- mice. In contrast to the human pANCA, both nuclear and perinuclear staining was found. Absorption of either human or mouse pANCA-positive sera with enteric bacterial antigens greatly reduced or abolished the specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in humans but also in IL10-/- mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens.