BACKGROUND Total parenteral nutrition (TPN) has been shown to affect liver function tests. Additional investigations in animals and humans have demonstrated that hepatic cytochrome P-450 content and enzyme activity are also affected. METHODS To review the literature on the effect of TPN on hepatic cytochrome P-450, an English-language literature search was performed using MEDLINE (1966 through 1993). RESULTS Studies in laboratory rats show that administration of dextrose, with or without amino acids, decreases the cytochrome P-450 content and the in vitro or in vivo microsomal oxidation rates of various drugs. The addition of lipid emulsions to TPN decreases oxidation rates for meperidine demethylase but does not affect ethoxyresorufin deethylase. Using immunoquantitation, it was shown that the components of TPN selectively affect specific hepatic P-450 enzymes. In humans, dextrose decreases antipyrine clearance, whereas amino acids and possibly lipids increase antipyrine clearance. However, the effects of protein-calorie malnutrition in these studies obscure the results. CONCLUSIONS Possible mechanisms for the reduction of hepatic cytochrome P-450 seen during TPN administration include altered gastrointestinal hormone response, mucosal barrier, and the effect of sepsis. Additional studies are needed to determine the actual mechanisms of hepatic cytochrome P-450 reduction observed during TPN.