Changes in hepatic α-glycerophosphate (α-GP) concentration have been measured following a variety of metabolic stimuli in normal rats and dogs. Rapid and reproducible variations in the concentration of α-GP were documented. Situations in which the liver was forced to channel carbons into new glucose formation were associated with a decrease in hepatic α-GP concentration. This relationship was independent of both the experimental agent employed and the peripheral glucose concentration, and was thought to result from increased conversion of α-GP to glucose as well as from decreased production of α-GP secondary to the demand for increased hepatic glucose formation. In contrast, experimental conditions which inhibited formation of hepatic glucose were associated with increases in hepatic α-GP concentration, and, as before, the changes were not dependent upon the specific agent employed or the plasma glucose concentration. This rise in hepatic α-GP was interpreted as being the result of increased conversion of 3-carbon fragments into triglyceride synthesis, and the possible relevance of this observation to the phenomenon of hypertriglyceridemia in man was discussed. Finally, the relative lability of hepatic α-GP concentration lends further support to the notion that α-GP may play an important role in regulating hepatic intermediary metabolism.