An oral dose of 14C-bupranolol hydrochloride was well absorbed by humans (100 mg), dogs (1 mg/kg), and rhesus monkeys (1 mg/kg). These species excreted 87.8 and 3.5%, 81.1 and 13.6%, and 92.9 ad 5.0% of the 14C-dose in urine and feces, respectively, mainly in 12 or 24 hr. Mean plasma levels of 14C, which appeared to be almost entirely associated with a single metabolite, peaked at 1 hr in humans (1.6 micrograms-equiv./ml) and dogs (1.6 micrograms-/ml) and at 2 hr in monkeys (0.8 micrograms-equiv./ml). Concentrations initially declined with similar half-lives (about 1.5 hr) in all three species. Biliary excretion of 14C occurred in the animal species in which also peak plasma 14C levels exceeded those in most tissues. Unchanged bupranolol was not detected in plasma; the peak plasma and urinary 14C was mainly associated (greater than 90% in humans) with a metabolite produced by oxidation of the aromatic ring methyl group of bupranolol to a carboxyl group.