The effect of protein deprivation on the activities of hepatic drug-metabolizing enzymes was studied in young rats whose mothers had previously been on a protein-restricted diet during pregnancy. Dietary protein deficiency (5% lactic casein as the protein source) lowered the amount of cytochrome P-450 and the activities of epoxide hydrolase and UDP-glucuronosyltransferase (UDPGT) (l-borneol as the substrate) by about 45, 63, and 48%, for the first 8 weeks, respectively. Interestingly, UDPGT estimated with p-nitrophenol as the substrate was far less affected than that estimated from l-borneol glucuronidation. This finding provides further evidence of the heterogeneity of UDPGT. Restoration of a balanced diet for 15 days following protein deprivation quickly restored cytochrome P-450 and enzyme activities to control values. Our experiments showed that the development of drug-metabolizing enzymes was changed more by the diet in young rats than in older rats. This could affect the toxicity of drugs that are normally metabolized by these pathways.