The effects of the NMDA blockers, AP5 and MK-801, were assessed in two spatial tests. AP5 (10 micrograms in 2 microliters ICV, N = 6), or MK-801 (0.07 mg/kg IP, N = 6), significantly increased open-field activity in male Long-Evans rats in two 3-min tests (Days 1 and 2) compared to control groups receiving equal volume saline injections (N = 12). In the Morris milk maze, NMDA blockade significantly impaired acquisition performance on two blocks of six trials, which followed each open-field test. Only control animals showed evidence of acquisition on a drug-free retention test assessing latency to reach the expected platform area and number of crossings in the area on Day 4. Retention was tested in control animals under NMDA blockade on Day 6. There was no effect of NMDA blockade on retention in the Morris milk maze. These results support the hypothesis that NMDA receptors are critical for the initiation of synaptic modification underlying place learning, but are not necessary in synaptic transmission during retrieval of place information.