Hepatic drug-metabolizing capacity was investigated in 56 diabetics. The antipyrine test was selected as an in vivo index, since its kinetics indirectly reflect the metabolically active liver mass. Hepatic cytochrome P-450 (P-450), determined from the biopsy samples, was used as an in vitro parameter, since it is a direct measure of microsomal drug-metabolizing enzyme activity. There was a wide interindividual variation in the indexes of drug metabolism in the diabetics: 40 fold in P-450 content and eightfold in antipyrine metabolism. P-450 levels were higher and antipyrine metabolism faster in the subjects with normal liver than in those with fatty liver, parenchymal inflammatory changes, or cirrhosis. Thus the in vivo and in vitro parameters of drug metabolism were related to the alterations in liver histology. On the other hand, the diabetes per se did not seem to alter the drug-metabolizing capacity of the liver. Also, drug metabolism in diabetics classified by treatment regimen did not differ significantly.