Sixteen euthyroid patients with Graves' disease were given 1000 μg of thyrotropinreleasing hormone (TRH) intravenously and changes in serum thyrotropin (TSH) concentrations were measured. In the same patients, before the time of TRH injection, serum thyroxine, serum free thyroxine, serum triiodothyronine and serum free triiodothyronine concentrations as well as thyroxine turnover were determined. Six patients had not previously been hyperthyroid as far as could be ascertained, and 10 had become euthyroid after treatment for hyperthyroidism. Five of the 16 patients did not respond to intravenous TRH with a rise in serum TSH concentration. The mean values for serum thyroxine, serum free thyroxine, serum triiodothyronine, serum free triiodothyronine and thyroxine turnover for the 5 TRH nonresponsive patients were not statistically different from those in the 11 TRH-responsive patients. In addition, a dissociation between thyroidal suppressibility and TRH responsiveness was observed in several patients. The mean basal serum TSH concentration, 0.8 ± 0.6 (sd) μU/ml, for the TRH-unresponsive euthyroid group was significantly less (p < 0.01) than that in the responsive group, 2.8 ± 2.2 (sd) μU/ml. TRH-unresponsiveness in euthyroid patients may be the result of a higher intensity of negative feedback at the pituitary level by circulating thyroid hormones or due to a separate abnormality in pituitary synthesis and/or release of TSH.