The influence and mechanism of action of T4 treatment on ethanol metabolism was investigated by the determination of ethanol elimination in intact rats and by the estimation of alcohol dehydrogenase and the microsomal ethanol oxidizing system activity in isolated rat liver. The rate of ethanol degradation was significantly decreased to 65% of control values in T4-treated rat liver. Similarly blood ethanol disappearance rate was significantly inhibited in thyrotoxic rats as compared to euthyroid animals. Hepatic alcohol dehydrogenase activity was reduced to 39% of control values as a result of T4 treatment; however, the microsomal ethanol oxidizing system activity was not affected. These data suggest that reduction in blood ethanol disappearance rate is associated with inhibition of hepatic alcohol dehydrogenase activity in thyrotoxicosis.