A specific anti-neutrophil antibody was recently described in primary sclerosing cholangitis and was detected using an indirect immunoalkaline phosphatase method. The present study examined the relationship of this antibody with respect to time, clinical activity, liver biochemistry, histology and ursodeoxycholic acid treatment. Fourteen patients with primary sclerosing cholangitis were followed up at regular intervals for 2 years. Clinical activity, liver biochemistry, histology and anti-neutrophil antibody titre were determined during the study period. A fluctuating course of the anti-neutrophil antibody was noted in both untreated patients and in those who were on ursodeoxycholic acid. This finding will have clinical implications if anti-neutrophil antibody is used to screen for potential primary sclerosing cholangitis in the future. The results suggest that several determinations of the antibody would need to be carried out over a period of time. No correlation was found between the antibody titre, clinical activity, liver biochemistry or histology. Anti-neutrophil antibody in primary sclerosing cholangitis probably has no pathogenic significance and is an epiphenomenon.