Significant compositional differences in protein and lipid content are present in currently available enteral nutrition preparations. Since variations in dietary protein and/or lipid have previously been shown to produce alterations in liver and gut drug metabolism, effects of five commonly used enteral nutrition regimens on several drug metabolic parameters were assessed in rats. Study formulations included: 1) Vivonex: low protein ‐no lipid; 2) High Protein Vivonex: normal protein ‐no lipid; 3) Vital: normal protein ‐normal lipid; 4) Sustacal: high protein ‐high lipid; 5) Isocal: normal protein ‐high lipid. Hepatic and intestinal microsomes were prepared after a continuous 7‐day intragastric infusion of one of the formulations, and measurements of cytochrome P‐450 content and assays of drug metabolizing activity were performed. No differences in intestinal microsomal cytochrome P‐450 content or meperidine demethylase activity were seen among the various alimentation groups. However, significantly decreased amounts of cytochrome P‐450 and reduced meperidine demethylase and pentobarbital hydroxylase activity were present in hepatic microsomes of animals receiving the lipid‐poor Vivonex and High Nitrogen Vivonex preparations compared to the other alimentation groups. These data suggest that the composition of enteral nutrition formulations may significantly impact on hepatic function and specifically that the presence of lipid in such preparations may be important for maintaining normal levels of hepatic drug metabolism.