The systemic bioavailability of propranolol was evaluated following oral and transdermal administration in rabbits. Using a four-way crossover study, the bioavailability of propranolol following oral administration was determined to be 12.3 +/- 5.9%, indicating that propranolol is subject to extensive hepatic first-pass metabolism in rabbits. Transdermal delivery of propranolol, via an adhesive delivery device, resulted in a bioavailability of 74.8 +/- 10.1%, indicating that the transdermal delivery of propranolol can significantly increase systemic bioavailability over oral administration. Skin irritation studies indicated that neither propranolol nor the adhesive used in the device caused any appreciable skin irritation.