Striatal microdialysis was performed in rats exposed to carbon monoxide (CO). Extracellular changes of dopamine, serotonin, and their metabolites were monitored before and after CO exposure at 15-min intervals by HPLC analysis. After CO exposure, extracellular dopamine increased (3.8 times that of baseline), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (by 20-25% of baseline). The decrease in HVA at individual time points, however, was not significant. After a transient increment of the dopamine, it was cleared from the extracellular fluid within 45 min and reached a stable level. Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) showed a pattern different to that of dopamine and its acid metabolites, i.e., the changes in extracellular levels were small. Pretreatment with dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, 45 min before CO exposure antagonized the changes in the extracellular concentration of DOPAC. However, the change in dopamine levels was not antagonized by pretreatment with MK-801. MK-801 itself had no effect on the levels of monoamines. Therefore, NMDA receptors may not have an important role for regulating striatal dopamine neurons in hypoxic condition.