Determination of the ED50s of glucose and fructose, administered i.p., for antagonizing the antinociceptive action of morphine (4 mg/kg s.c. or 0.5 micrograms i.t.) and determination of the ED50s for i.t. morphine after i.p. pretreatment with saline, glucose (5 g/kg) or fructose (5 g/kg) in the mouse tail-flick test indicated that fructose was more potent than glucose in antagonizing antinociception after either route or morphine administration. It is concluded that the antagonism of morphine-induced antinociception by glucose and fructose is due to a direct effect of these sugars or their metabolic products within the central nervous system.