Drug discrimination procedures in mice are used to study the neuropharmacology of a wide variety of drugs. In C57 B1/6 mice, infection with the LP-BM5 murine leukemia virus leads to a syndrome (murine acquired immunodeficiency syndrome-MAIDS) characterized by immunocompromise, neurochemical alterations, and learning and memory deficits. Because the neurochemical and behavioral changes suggest that altered glutamatergic neurotransmission follows LP-BM5 infection, we studied the effects of infection on discriminative stimulus properties of phencyclidine (PCP), a Ca2+ channel blocker at NMDA receptors. We also tested D-amphetamine and dizocilpine to assess the specificity of the discrimination. As expected, dizocilpine produced PCP-like responding. After animals were trained to discriminate PCP from saline, they were inoculated with LP-BM5 and the PCP dose-response functions repeatedly determined. The potency of PCP in this procedure was unchanged 3 weeks after infection, but was increased approximately fivefold 6 and 9 weeks after infection. Amphetamine 9 weeks after inoculation did not produce PCP-like responding, showing that the results were not caused by a loss of specificity of the discrimination. The time course for changes in PCP potency is similar to those of other behavioral and neurochemical changes reported after LP-BM5 infection. The results are consistent with an action of LP-BM5 infection at glutamatergic synapses.