Abstract Objective To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism. Animals 8 conditioned, random-source, young adult, female cats. Procedure Propranolol was administered IV as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 μg/kg of body weight, SC, once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 ± 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography. Results In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 ± 7,900 min·μg/L vs 15,911 ± 1,400 min · μg/L) after IV administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 ± 57,600 min·μg/L vs 226,811 ± 112,000 min·μg/L) and peak serum propranolol concentration (651 ± 247 μg/L vs 1191 ± 590 μg/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 ± 28% vs 137 ± 73%) and decreased total body clearance (58 ± 27 ml/min/kg vs 30 ± 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 ± 38 minutes vs 157 ± 71 minutes). Clinical Relevance Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats. (Am J Vet Res 1997;58:398–403)