The incubation of whole blood with fructose-1,6-diphosphate (FDP) entails a statistically significant increase of intraerythrocytic FDP together with a decrease of blood glucose. The increase is not significant when equimolar amounts of fructose plus twice molar phosphate are used. The effect of FDP is decreased in the presence of an excess of oxygen. FDP added to the whole blood is removed from plasma by the activity of plasma enzymes and by the presence of blood cells as well. No specific interaction of FDP with plasma proteins seems to occur and the effects of FDP addition last longer than is compatible with the presence of FDP in the plasma.