1. Lofepramine labelled with 3H in the dihydrodibenzazepine moiety and 14C in the chlorobenzene moiety was given orally to rats (20 mg/kg), dogs (3 mg/kg) and man (2 mg/kg).2. In dogs and man blood isotope levels were determined by combustion. In both species the 14C-levels were higher than the 3H-levels during the first 6 h after dosing. Later more 3H was found. 3. In all three species most of the 14C activity was rapidly excreted in the urine as the glycine conjugate of p-chlorobenzoic acid. 4. No significant species difference in the urinary excretion of 3H-labelled metabolites was found and the major metabolites were 2-hydroxydesmethylimi pramine, 2-hydroxyiminodibenzyl and desmethylimipramine. 5. Considerable amounts of desmethylimipramine were found in faeces of dog and man but not rat. This differnece is discussed. 6. By the ultrafiltration technique, lofepramine was found to be bound to plasma proteins of the rat, dog and man to an extent of 99%.