Antithyroid drugs are a mainstay of therapy of hyperthyroidism, especially when it is due to Graves' disease. Although antithyroid agents are generally safe, side effects may limit their useful' ness in some patients. Side effects are classified as minor and major, based on their degree of morbidity. All side effects are more common at higher doses of methimazole (40 mg/day or more), but there is no apparent dose relationship for propylthiouracil (PTU). The most common minor side effects include cutaneous eruptions, arthralgias, and gastrointestinal upset, which develop in up to 5% of patients at usual doses. Hair loss, sialadenitis, myopathy, and abnormalities of taste and smell also have been described. The common major side effects are agranulocytosis (frequency 0.1-0.4%) and frank polyarthritis. Severe systemic vasculitis or drug-induced lupus (often an-tineutrophil cytoplasmic antibody positive) are associated with PTU. Hepatic toxicity with methimazole is cholestatic in nature and not as severe as the potentially life-threatening hepatocellular reactions that are seen with PTU. Hypoprothrombinemia and the insulin autoimmune syndrome are exceedingly rare major side effects (C) 1999 Lippincott Williams & Wilkins, Inc.