In vitro metabolism of the aromatic ketone propiophenone and its nonaromatic isomer phenylacetone was studied using fortified 12 000 × g supernatants of liver homogenates from rat and rabbit. Reduction to the corresponding alcohols was the major metabolic route observed, although aliphatic C-hydroxylation and alcohol dehydrogenation also occurred. Marked differences were observed in the amounts of carbonyl reduction of the substrates, which was dependant on the species as well as the cofactor employed. Using rat liver preparation, phenylacetone was reduced to 1-phenyl-2-propanol much more efficiently with an NADH-fortified system than when NADPH was used whereas in rabbit, extensive reduction occurred in the presence of either cofactor. Reduction of propiophenone to 1-phenyl-1-propanol by rat liver preparation was slightly greater in the presence of NADH than with NADPH; the converse was observed in rabbit.Aliphatic hydroxylation of propiophenone to 2-hydroxy-1-phenyl-1-propamine was also a significant metabolic pathway in both species, with NADPH being the more efficient cofactor, but C-1 hydroxylation of phenylacetone to 1-hydroxy-1-phenyl-2-propanone occurred only to a minor extent. Small amounts of 1-phenyl-1,2-propanedione, as well as both erythro and threo isomers of 1-phenyl-1,2-propanediol, were also identified as metabolites in both species. Similar metabolic studies were carried out on the alcohols 1-phenyl-1-propanol and 1-phenyl-2-propanol and again the nature and quantities of metabolites isolated showed both species and cofactor dependancies.