Patients with untreated hyperthyroidism due to Graves' disease have a proportionally greater increase in the serum T3 than in the T4 concentration and, therefore, have an elevation of the serum T3 to T4 ratio. The aim of this study was to investigate the alterations of the serum T3 to T4 ratio in relation to the outcome of antithyroid drug therapy. Of 47 patients with hyperthyroid Graves' disease, 37 patients had a serum T3 to T4 ratio greater than 20 ng/micrograms before therapy (normal range, 12-20; mean, 16.0). In 7 of 37 patients, serum T3 to T4 ratios remained high during a 2-yr course of antithyroid drug therapy, and in 6 of them (86%), hyperthyroidism recurred after cessation of drug therapy. In the remaining 30 patients, the initial high serum T3 to T4 ratios decreased to normal (less than 20) during treatment, and 15 of them (50%) had a remission of the disease after cessation of the drug. Of the 10 patients with initial serum T3 to T4 ratios within the normal range, this ratio remained normal during treatment, and 8 (80%) had a remission. Goiter size was larger in patients with high serum T3 to T4 ratios, and a reduction of goiter size occurred in some patients (57%) with decreasing serum T3 to T4 ratios. The serum T3 to T4 ratio is a simple and useful predictor of the outcome of antithyroid drug therapy in patients with Graves' disease. A ratio greater than 20 throughout therapy indicates that the likelihood of relapse is high, and a ratio below 20 either initially or during therapy is an indicator of prolonged remission.