The sequential clinical and laboratory (serum T4, T3 and rT3 concentrations) effects of propranolol were studied in 21 hyperthyroid patients. The amount of propranolol required to achieve clinical compensation ranged from 240 to 400 mg/day. For two patients, 480 mg/day, the maximal dose used, did not produce clinical compensation. The only significant changes in serum iodothyronines was detected in the 9 patients compensated with 240 mg/day. T3 decreased from 362 to 299 ng/dl (P less than 0.05) and the rT3/T3 molar ratio increased from 3.4 to 6.5 (P less than 0.025). The increases of rT3 from 113 to 168 ng/dl and of the rT3/T4 molar ratio from 6.7 to 10.8 were not statistically significant (P = 0.052). A slight decrease of serum T3 and increase of serum rT3 occurred during the first or second week in the other patients but the changes were not sustained over the whole period of treatment. These results show that the effects of propranolol on hyperthyroidism were independent of its transitory effects on the peripheral metabolism of thyroid hormones, thus providing further support for the current view that the clinical improvement of hyperthyroid patients on propranolol therapy is probably due to beta-adrenergic receptor blockade. A small percentage of thyrotoxic patients may not show clinical improvement even when propranolol doses of more than 400 mg/day are used.