The activity of rat liver tryptophan pyrrolase (EC 1.13.11.11) is inhibited by chronic ethanol administration by a mechanism not involving a defective apoenzyme synthesis nor a decreased cofactor availability, but associated with an increased liver [NADH] and [NADPHJ (Badawy & Evans, 1973a,b, 1975). These two reduced nucleotides are allosteric inhibitors of the activity of the purified enzyme (Cho-Chung & Pitot, 1967), and their possible involvement in the inhibition by ethanol is suggested by the finding (Badawy & Evans, 1975) that the latter can be reversed by regeneration of liver NAD+ or NADP+ in vivo or by the addition of these oxidized nucleotides in vitro. Mnrrland (1974) has, however, suggested that ethanol acts chronically by inhibiting apo-(tryptophan pyrrolase) synthesis because the drug treatment inhibits the dexamethasone induction of the enzyme activity in the isolated perfused rat liver. However, we have found (Badawy & Evans, 19736) that the cortisol induction of the pyrrolase activity in intact rats is not impaired by chronic ethanol administration. A possible explanation of the finding by Mnrrland (1974) is that his ethanol-treated rats have also been given sucrose, which inhibits the pyrrolase activity (Badawy & Evans, 1976~). We have also shown in this latter study that sucrose acts via glucose, and that the latter sugar inhibits the pyrrolase activity by an NADHand NADPH-mediated mechanism. Moreover, we have shown that the decreased cortisol induction of the enzyme activity in glucose-pretreated rats is due to inhibition of activity and not synthesis of the apoenzyme. Since the results of experiments by Mnrrland (1974) do not permit an interpretation of a possible ethanol effect in the absence of sucrose, we have compared the cortisol induction of the pyrrolase activity in rats chronically treated with water, ethanol or sucrose. Locally bred male Wistar rats (body wt. was lOOg at the start of the experiments) were allowed free access to cube diet 41B and one of the foliowing three drinking fluids for 28-31 days: water, sucrose (9%, w/v) or ethanol [ 5 % (v/v) for 2 days, 7.5% for 2 further days and finally 10x1. Some of these rats also received, 4h before death, an