Fifty-six sera from patients with autoimmune thyroiditis and 33 sera from patients with MPO-ANCA were examined in order to ascertain whether a cross reactivity between MPO-ANCA and anti-thyroperoxidase (aTPO) was present. Sera from 20 healthy donors aTPO and aMPO negative were used as control. About 95% of heat inactivated sera from patients with autoimmune thyroiditis and from controls gave positive results (atypical pANCA pattern) on ethanol-fixed neutrophils. The prevalence of positive results was significantly lower when unheated aTPO positive sera were used (17.8%). On the other hand, only 9% of sera with MPO-ANCA were positive on cryostatic sections of human thyroid. Indirect immunofluorescence tests (IF) on human neutrophils with MPO defect were negative with sera from patients with MPO-ANCA, but uninactivated sera with aTPO and positive for pANCA on normal neutrophils showed a very high prevalence of positive results (90%). According to our data only few sera positive for aTPO recognize "normal" MPO, but the majority of sera from patients with autoimmune thyroiditis and positive for pANCA on normal neutrophils recognize also an "abnormal" MPO. On the other hand MPO-ANCA usually recognize epitopes presently only on the normal enzyme, a small proportion of these autoantibodies can react with TPO. Heat inactivated sera give false positive results for pANCA on ethanol fixed human neutrophils.