The effect of alcohol intake on the operation of the pentose cycle and NADPH generation will be studied in rats in vivo and in vitro. Chronic alcoholic rats will be used when "drunk" (high blood alcohol) and "sober," with control diet substituted overnight for that with ethanol. Methods to calculate the pentose cycle developed by us will be used. For in vivo studies rats will be infused with 2-3H glucose and 1-14C acetate, and glucose isolated. The formation of NADPH will be calculated from the turnover of 2-3H glucose and the distribution of 14C in carbons 1,2 and 3 of glucose. Experiments in vitro will be with isolated hepatocytes from chronic alcoholic "drunk" and "sober" and control rats. The cells will be incubated with 2-3h glucose and 1-14C galactose, and the effect of ethanol on the pathways of glucose-6P and NADPH yield will be determined by novel procedures. The role of NADPH production by malic enzyme will be explored. The source of NADPH for the hydroxylation of aniline and hexobarbitol in alcoholic and control rats will be examined.