The acute effects of 0.05 mg/kg MK-801 on spatial learning and memory in male mice were studied using a modified hole board food search task. Dose-response sensorimotor and activity tests suggested that this dose of MK-801 did not induce significant nonassociative effects. Mice were trained on the hole board using a massed trials protocol to learn the location of a hole baited with a food reward among four corner holes. Retention was tested 24 h later. Mice were split into two groups matched according to acquisition scores. The following week, mice injected with 0.05 mg/kg MK-801 30 min before being trained to a different baited hole were significantly impaired in acquiring a new baited hole location compared to saline-treated mice, although retention performance was unaffected. The same result was found in another experiment in which treatments were crossed over, and a different version of the task was used. However, in another experiment, 0.05 mg/kg MK-801 did not impair performance when the hole board task was well learned.