A patient on a regimen of 400 mg/day of propranolol hydrochloride was observed to have elevated thyroxine (T4) and free T4 levels with a normal thyrotropin response to protirelin. This led us to study the prevalence of hyperthyroxinemia in 14 consecutively treated patients with hypertension on daily doses of propranolol of 320 mg or more. Four of 14 patients had elevated serum T4 levels. As a group, the patients on propranolol therapy had higher serum T4 levels, free T4 indices, and triiodothyronine levels than did healthy controls. The use of high-dosage propranolol may be associated with euthyroid hyperthyroxinemia and be a source of diagnostic confusion. All patients receiving therapy with high-dosage propranolol should undergo protirelin testing before one can conclude that their elevated thyroid hormone levels are due to hyperthyroidism.