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1. Rats fed on purified synthetic diets have a markedly lower cytochrome P-450 concentration and hydroxylating enzyme activity in liver microsomal fraction than rats fed on stock pellets. 2. When both groups are treated with phenobarbitone the difference is even greater, the purified diet allowing only 50% of the cytochrome P-450 concentrations of controls. 3. Addition of herring oil, linoleic acid or 0.1% oxidized sitosterol to the diets allows induction of cytochrome P-450 to take place. 4. Addition of coconut oil to the diet does not permit induction of cytochrome P-450. 5. The interactions between dietary protein and the lipid substances are explored. 6. The mechanism of induction of microsomal hydroxylation enzymes by drugs is discussed in the light of these requirements.