Recent studies reveal at least three receptor subtypes for excitatory amino acid (EAA) neurotransmitters. Activation of one of these, the N-methyl-D-aspartate (NMDA) receptor-channel complex, has been strongly implicated in neuronal mechanisms of several important brain processes, including learning and memory. As NMDA receptors are highly sensitive to extracellular magnesium (Mg++), we tested whether in vivo concentrations of this ion are sufficient to suppress NMDA-receptor-mediated responses. We show that slow, local microinfusion of Mg(++)-free artificial cerebrospinal fluid onto noradrenergic locus coeruleus (LC) neurons reveals an NMDA-receptor-mediated component of their response to a sensory stimulus. This is the first demonstration that the in vivo concentration of extracellular Mg++ ions suppresses synaptically mediated NMDA receptor activation. We also present evidence that unmasking this NMDA receptor activity induces prolonged enhancement of the EAA-mediated sensory response of LC neurons.