Direct injections of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), an AMPA/quisqualic acid receptor agonist, into the medial or posterior zona incerta (ZI) produced a marked stimulation of locomotor activity accompanied by a postural change. Similar responses were obtained by injection of kainic acid (KA) into the same areas. The behavioral effects of AMPA and KA were antagonized by coinjection of 6,7-dinitroquinoxaline-2,3-dione (DNQX), and non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist. In contrast, injections of NMDA or ibotenic acid failed to significantly stimulate locomotor activity. These results suggest that the AMPA/kainate glutamate receptor subtypes in the zona incerta may have a functional role in regulating locomotor activity.