Glycogen metabolism in frog (Rana ridibunda) liver is subject to seasonal variations. Hepatic glycogen and glycogen synthase levels are highest in the fall and winter months and lowest in the summer months, whereas glycogen phosphorylase activity is highest in spring and summer and lowest in fall and winter months. Blood glucose levels show a clear increase during the months of March, June-July and November over the mean level for the rest of year (19.0 +/- 5.5 mg glucose/100 ml serum). Results indicate that the animal accumulated glycogen in the fall to be consumed during the winter. Glycogen levels are in direct proportion to glycogen synthase activity levels (I-form and total activity) and in inverse proportion to glycogen phosphorylase (phosphorylated form) activity levels, which would suggest that these enzymes exercise a direct control over glycogen levels.