14C-labeled mepindolol was rapidly and almost completely absorbed in the rat and dog after oral administration of 0.4 mg/kg, achieving maximum concentrations in the plasma after 1-2 hr. In the rhesus monkey, absorption was distinctly slower. Higher doses (25 mg/kg) given to rats and dogs exhibited maximum levels at 6 hr. The bioavailability of low doses was 1-2% in the rat and 40% in the dog. Plasma levels of unchanged drug declined biphasically in the dog with half-lives of 8 min and 3 hr. Excretion of radioactivity was mainly biliary in the rat. In the dog, elimination was equal in feces and urine, and in the rhesus monkey it was mainly renal. Although in the rat and rhesus monkey 14C-active compounds were completely eliminated, substantial amounts of metabolites were retained in the liver of the dog even 10 days after administration. After repeated administration, labeled substances accumulated in the dog, reaching maximum concentrations in the liver.