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ADVANTAGE has been taken of the recent development of highly sensitive methods (LOWRY, PASSONEAU, SCHULZ and ROCK, 1961) to study the response of the individual pyridine nucleotides (NADf, NADH, NADP+, NADPHg) in the brain andliver of rats to a low tryptophan, niacin-free diet. The study of three pyridine nucleotide-dependent enzymes was included, prompted by the findings of BURCH et al. (1956,1960) that some flavin-dependent enzymes decrease in riboflavin deficiency.SINGAL, SYDENSTRICKER and LITTLEJOHN (1 948) measured the nicotinic acid levels in different tissues of rats on corn rations and found them to be subnormal in the brain, liver, and muscle of the deficient animals but normal in other tissues. BURCH et al. (1955) reported that rats fed low amounts of tryptophan and niacin had subnormal amounts of oxidized pyridine nucleotides in blood cells and liver. More recently, SPIRTES and ALPER (1 961) studied the diphosphopyridine nucleotide levels in the livers of niacin-deficient and protein-deficient mice. They found a decrease of both NAD+ and NADH in the liver of the niacin-deficient animals, with no change in the NAD+/NADH ratio. Animal preparat ionWeanling male rats of the Holtzman strain weighing 45-50 g were housed in individual metabolism cages. Once daily the animals were fed, and their weights were recorded.The basal diet described by BURCH et al. (1956) was used with the following modifications: (1) In order to decrease the tryptophan content of the diet, casein was reduced from 20 to 6.8 per cent and zein was added at a level of 13.6 per cent; (2) since zein is low in lysine as well as tryptophan, lysine was added to the diet at a level of 0.6 per cent; (3) the vitamin mixture was altered by omitting niacin and adding riboflavin at a level of 0.15 per cent to the vitamin mixture. The niacin-supplemented diet contained 8 mg of niacin per 100 g of basal diet. The animals were divided into three groups: (1) a deficient group consisting of seven animals that were offered the basal diet ad libiturn; (2) a weightcontrol group of eight animals receiving the niacin-supplemented diet in amounts just sufficient to keep their weights the same as those of the deficient animals; (3) a group of five animals receiving the niacin-supplemented diet ad libitum. The diet of this group was probably not entirely adequate because of the poor quality of zein as a dietary protein. The animals gained 25 per cent less weight than those