Efferent fibers from the nucleus accumbens (N.Acc.) to the substantia innominata and lateral preoptic region (SI/LPO) are believed to be essential for the supersensitive locomotor response to apomorphine in rats following 60HDA-induced denervation of the N.Acc., since destruction of cells within the SI/LPO eliminates this supersensitive response. In the present study, the neurochemical properties of this efferent projection were investigated. Injection of muscimol, a GABA agonist, directly into the SI/LPO produced a dose-dependent decrease in supersensitive locomotor activity at doses that did not alter baseline locomotion. Higher doses of muscimol actually produced a prolonged locomotor activation in all animals. These results suggest that the locomotor activation following stimulation of supersensitive dopamine receptors within the N.Acc. may involve a decrease in GABAergic activity at the level of the SI/LPO.