1. Metabolic acidosis was induced by feeding ammonium chloride to rats which were maintained on a carbohydrate diet for 48 h.
2. Fasting blood glucose was the same in acidotic and control animals, but there was an increase in liver glycogen in the former. Muscle glycogen was unchanged.
3. In vitro glycogenolysis was the same in liver slices from normal rats when incubated at a range of pH from 6·90 to 7·40.
4. The peak blood glucose in response to intraperitoneal injections of glucagon was the same in control and acidotic rats. The rate of disappearance of glucose was slower in acidotic rats both after the glucagon induced hyperglycaemia and after intravenously injected glucose.
5. Liver phosphorylase, total glycogen synthetase and the I form of this enzyme were unchanged in acidosis.
6. The data are compatible with the hypothesis that in the acidotic rat there is a block in glycolysis—possibly at the phosphofructokinase step.