We studied a new type of Graves' disease: rapidly progressive thyroid failure after painful attack in the thyroid gland. Four women with the mean (+/- SD) age of 51 +/- 3.2 years had newly diagnosed hyperthyroid Graves' disease. A severe painful episode developed in the thyroid glands of two patients and permanent hypothyroidism occurred spontaneously within 2 or 3 months thereafter. Two to three episodes of pain developed in the thyroid glands of the other two patients during antithyroid drug therapy. There was a transient rise in serum thyrotropin level after each painful episode and permanent hypothyroidism developed 6 to 8 months after the initial painful attack. The clinical picture is characterized by moderate to severe pain in the thyroid gland with tenderness. Patients responded to steroid or anti-inflammatory therapy. During painful attack, increased or normal thyroid radioiodine uptake, elevated levels of C-reactive protein, and an elevated erythrocyte sedimentation rate were found, but there was no cytological evidence of subacute thyroiditis. After painful attack, serum thyroid stimulation antibody began to decrease in three of the patients while thyroid stimulation blocking antibody developed in one patient. This is a rapid and self-destructive process of the Graves' thyroid gland, which appears to be associated with painful attack in the thyroid gland.