1. [2-14C]Prazosin is rapidly distributed into tissues of the dog including heart, lung and vascular tissues. 2. Urinary excretion by rats and dogs is low, biliary secretion being the major route of elimination. 3. Biotransformation of prazosin in the rat and dog occurs primarily by 6- or 7-O-dealkylation and subsequent glucuronide formation, and to a lesser extent via N-dealkylation. 4. Preliminary metabolic studies in man indicate a pattern of metabolites similar to that observed in dogs and rats.