OBJECTIVE Perinuclear antineutrophil cytoplasmic antibodies (pANCA) were found at high frequency in patients with primary sclerosing cholangitis and ulcerative colitis. In this study, to accumulate further evidence for the importance of genetic factors in pathogenesis of inflammatory bowel disease, sera of patients with inflammatory bowel disease and primary sclerosing cholangitis and their unaffected family members were tested for pANCA. METHODS Three hundred twenty-seven sera from 11 families of patients with primary sclerosing cholangitis, 43 families of patients with ulcerative colitis, 11 families of patients with Crohn's disease, and 11 healthy families were tested for pANCA in immunofluorescence on cytospin slides with isolated neutrophils. RESULTS pANCA were found in 82% of the patients with primary sclerosing cholangitis and in 25% of their relatives. In ulcerative colitis, 70% of the patients and 30% of their relatives had pANCA. pANCA were found only in low titers in 27% of patients with Crohn's disease and in 6% of their relatives. pANCA were not detected in members of healthy families. Only 16% of the patients with ulcerative colitis and their families and none of the patients with primary sclerosing cholangitis and their families were completely negative for pANCA. CONCLUSIONS These data show that pANCA may be a genetic marker in families of patients with ulcerative colitis and primary sclerosing cholangitis.