Eosinophil-derived neurotoxin (EDN) is released after activation and stimulation of eosinophils in allergic disease, which is a T(H)2-predominant condition. We previously reported that Graves' thyrotoxicosis develops or relapses after an attack of allergic rhinitis. In this study, to confirm the relation between Graves' disease and the allergic condition, we determined the serum level of EDN in 30 untreated patients with Graves' disease, 50 patients with Hashimoto's thyroiditis, and 39 normal controls. Compared to the serum level in normal subjects (30.1 +/- 15.6 ng/mL), EDN was increased in untreated patients with Graves' disease (52.4 +/- 27.6 ng/mL), but not in patients with Hashimoto's thyroiditis (thyrotoxic, 30.9 +/- 13.4 ng/mL; euthyroid, 30.0 +/- 11.9 ng/mL; hypothyroid, 23.4 +/- 10.2 ng/mL). A significant correlation was observed between the EDN level and the serum activity of thyrotropin (TSH) receptor antibody (r = 0.541, p < 0.0001). These data suggest that the allergic condition is closely related to Graves' disease and that a T(H)2-type immune response is crucial in the pathogenesis of Graves' disease.