Conditioned flavor preferences (CFP) are elicited by sucrose and fructose relative to saccharin in rats and inbred mice. Whereas dopamine, but not opioid receptor antagonists interfere with the acquisition (learning) and expression (maintenance) of sugar-CFP in rats, these antagonists differentially affect acquisition and expression of sucrose- and fructose-CFP in BALB/c and SWR inbred mice. Given that NMDA receptor antagonism with MK-801 blocks acquisition, but not expression of fructose-CFP in rats, the present study examined whether MK-801 altered the expression and acquisition of sucrose- and fructose-CFP in BALB/c and SWR mice. In expression experiments, food-restricted mice alternately consumed a flavored (CS +, e.g., cherry, 5 sessions) 16% sucrose or 8% fructose + 0.2% saccharin solution and a differently-flavored (CS −, e.g., grape, 5 sessions) 0.2% saccharin solution. 2-Bottle CS choice tests occurred following vehicle or MK-801 at doses of 100 or 200 μg/kg. MK-801 mildly reduced the magnitude of the expression of sucrose- and fructose-CFP in BALB/c mice, and blocked the expression of fructose-, but not sucrose-CFP at the high dose in SWR mice. In acquisition experiments, groups of BALB/c (0, 100 μg/kg) and SWR (0, 100, 200 μg/kg) mice were treated prior to acquisition training sessions that was followed by 2-bottle CS choice tests without injections. MK-801 (100 μg/kg) eliminated acquisition of sucrose- and fructose-CFP in BALB/c, but not SWR mice. The 200 μg/kg MK-801 dose eliminated acquisition of sucrose- and fructose-CFP in SWR mice. Thus, NMDA receptor signaling is essential for the learning of both forms of sugar-CFP in both strains with BALB/c mice more sensitive to MK-801 dose effects.