The IgG subclass distribution of anti-thyroid peroxidase (TPO) antibodies in patients with chronic thyroiditis and in healthy subjects has been investigated. Anti-TPO antibodies in sera of patients with chronic thyroiditis were predominantly associated with IgG1, with a lesser contribution by IgG4 and IgG3. In contrast, anti-TPO antibodies of healthy subjects were exclusively associated with IgG4. Since structural differences in IgG subclasses reflect differences in their biological roles, these findings suggest that the role of anti-TPO antibodies in patients may differ from that in healthy subjects.