The effects of chronic ethanol ingestion on a preparation of liver glycogen phsophorylase have been studied. A coupled assay in the direction of glycogenolysis was used. In the absence of AMP, a significant decrease in specific activity was observed in both males (19%) and females (30%). AMP additions stimulated phosphorylase activity and completely obliterated the ethanol-induced decreases in both sexes of animal. Kinetic studies, done in the absence of AMP, showed that only the apparent Vmax had been altered by ethanol. These data suggest that decreases in liver glycogen after chronic ethanol ingestion may not be related to the specific activity of glycogen phosphorylase. Using both glucose and caffeine as negative effectors, addditional studies demonstrated that the inhibitory effects of caffeine had been altered by ethanol in both males and females and that the inhibitory effects of glucose had been altered only in females. Even though the specific activity for phosphorylase did not directly implicate this enzyme in the ethanol-induced decrease in liver glycogen stores, the latter data regarding glucose and caffeine suggest that chronic ethanol ingestion has altererd this enzyme and that differences exist between males and females.