Glucose was found to impair the antiviral activity of rabbit interferon (IFN) in RK-13 cells. This impairment was dependent on the glucose concentration: A pronounced impairment was observed at the concentration of 30 mg of glucose/ml, the maximum concentration which produced neither morphological changes of cells nor diminution of overall macromolecular synthesis. Maximal impairment was seen when glucose was added to the IFN-treated RK-13 cells early during the development of antiviral activity. Furthermore, glucose decreased the extent of induction of 2',5'-oligoadenylate synthetase by IFN. Of six different monosaccharides examined, only fructose had the same anti-IFN effect as glucose.