The pharmacokinetics of oral propranolol were studied during chronic treatment in six patients when thyrotoxic and again when euthyroid. The mean total plasma propranolol steady-state concentration was 42% lower when the patients were thyrotoxic. After treatment of thyrotoxicosis there was a fall (P less than 0.05) in the oral clearance of both total (4.2 +/- 0.6 to 2.7 +/- 0.4 L/min, mean +/- SEM) and free (30.5 +/- 4.7 to 25.5 +/- 4.1 L/min) propranolol although the half-life of propranolol did not change significantly. The free fraction of propranolol was higher (p less than 0.05) in the thyrotoxic (14.2% +/- 1.3%) than in the euthyroid (11.4% +/- 0.8%) state. These results suggest that the pharmacokinetics of propranolol are significantly altered in thyrotoxicosis.