The objective of this stud)' was to investigate ~f the altered 2El drug metabolism capaci~' in rats is due to effi, cts of dietar), zinc deficiency on the expression of hepatic microsomal P450 2El in rats. Rats were given free access to either a zinc-adequate diet or a zinc-deficient diet for 3 weeks. A second control group, the pair-fed control, was also included. At the end of the .feeding trial, each dietary group was .further divided into the drug control and ethanol treatment group. Ethanol (EtOH, 8 mL/kg bod), weight, intubation) was given once a day for 3 consecutive days. Within the drug control group, zinc deficiency reduced total P450 concentration but had no effect on the level of NADPH-P450 reductase, 2El protein, and 2El mRNA. 2El activity, which was indicated by N-nitrosodimethylamine demethylase ( NDMA ), aniline hydroxylase ( AH ), and p-nitrophenol hydroxylase ( NH ) activity, was also not affected by dietary zinc deficienc)~ The NDMA demethylase activit)' and 2El mRNA level were higher in zinc pair-fed rats than in zinc-adequate rats. EtOH treatment induced total P450 concentration in zinc-adequate and zinc-deficient rats and NADPH-P450 reductase level in zinc-adequate rats. 2El activity was induced by EtOH, while the level of 2El protein and 2El mRNA was unchanged, bl conclusion, the constitutive expression of hepatic microsomal 2El was not affected by zinc deficient')' per se; however, the prolonged severe depression of feed intake caused by zinc deficiency increased the level of 2El mRNA in rats. An acute EtOH treatment markedly induced 2El activio' without afj'ecting the level of 2El protein and mRNA.