A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in sheep as part of a study of the ability of the food-producing species to metabolize drugs. The following DME and components were measured in this study: cytochromes P-450 and b5 and NADPH and NADPH-dependent reductases associated with each of these cytochromes; cytochrome P-450-mediated reactions, including aniline and coumarin hydroxylases, aminopyrine N-demethylase, and 7-ethoxycoumarin 0-deethylase; a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase with dinitrochlorobenzene and dichloronitrobenzene as substrates. Amounts or activities of most of these components and enzymes increased up to and beyond the time of weaning. Amount of cytochrome b5 and uridine diphosphoglucuronic acid transferase activity were not affected by age, whereas NADPH cytochrome c (P-450) reductase activity actually decreased after weaning. In some instances (eg, coumarin hydroxylase, cytochrome P-450, and dinitrochlorobenzene-glutathione-S-transferase), differences from preweaning DME values were observed only after sheep were greater than or equal to 6 months old. All other DME activities were definitely increased, compared with the values in lambs before weaning (0 to 12 weeks old). Approximately a third of the sheep studied had some type of clinical disease that might have affected the DME activities. Diseases were classified as sore mouth, pneumonia, foot rot, parasitism, and systemic bacterial infections. Except in a few instances, these diseases had minimal effect on DME activities measured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)