The effects of infusing N-methyl-D-aspartate (NMDA), and the specific NMDA receptor antagonist D-2-amino-5-phosphono-propionic acid (D-AP5) into rat hippocampus and striatum on extracellular dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied using intracerebral microdialysis. In striatum NMDA increased DA extracellularly in a concentration-dependent manner. Against a 10 microM concentration of NMDA the increase in striatal DA was opposed by D-AP5 (10 microM in all experiments), which when infused alone significantly reduced DA concentration. Infusion of NMDA altered DOPAC level in a complex manner, with 10 microM concentration causing a significant increase 2 h after infusion, while 100 microM NMDA caused a transient decrease in the metabolite. None of treatments altered striatal dialysate HVA. In hippocampus NMDA infusion decreased dialysate DA in a concentration-dependent manner, and the decrease caused by 10 microM NMDA was reversed by D-AP5. When given alone the antagonist was without effect. NMDA infusion elevated hippocampal dialysate DOPAC and HVA, while HVA was decreased following D-AP5 infusion. These data indicate that DA release is regionally controlled by excitatory amino acids, but in differential manner.