Injections of amphetamine into the nucleus accumbens increased locomotor activity of rats. Subsequent injections of procaine into the midbrain, in the region of the pedunculopontine nucleus, significantly reduced the amphetamine-induced locomotor activity. Control experiments showed that procaine injections into the contralateral pedunculopontine nucleus had little or no effect, as well as ipsilateral injections dorsal and ventral to the pedunculopontine nucleus. These findings suggest that release of dopamine from amphetamine injections into the accumbens gives rise to ipsilateral descending influences on the region of the pedunculopontine nucleus, a major component of the mesencephalic locomotor region. Descending influences from the nucleus accumbens to mesencephalic locomotor region may serve as a link for limbic-motor integration in behavioral response initiation.