The efferent connections of the brain stem nucleus tegmenti pedunculopontinus were studied in the rat using the techniques of anterograde and retrograde transport of the enzyme horseradish peroxidase, laying particular emphasis on that part of pedunculopontinus which receives direct descending projections from the basal ganglia and related nuclei. In a preliminary series of experiments horseradish peroxidase was injected into either the entopeduncular nucleus or the subthalamic nucleus and, following anterograde transport of enzyme, terminal labelling was identified in nucleus tegmenti pedunculopontinus, surrounding the brachium conjunctivum in the caudal mesencephalon. In a subsequent series of experiments, horseradish peroxidase was injected into that region of nucleus tegmenti pedunculopontinus which receives entopeduncular and subthalamic efferents and its efferent projections were studied by anterograde transport of the enzyme. The results indicate that nucleus tegmenti pedunculopontinus gives rise to widely distributed efferent projections which terminate rostrally in mesencephalic, diencephalic and telencephalic structures and caudally in the pontine tegmentum. In the mesencephalon, terminal labelling was found in the pars compacta of the ipsilateral substantia nigra and sometimes in the adjoining ventral tegmental area. Labelling was also found in the ipsilateral half of the periaqueductal grey. In the diencephalon terminal labelling occurred bilaterally in the subthalamic nucleus and ipsilaterally in the intralaminar nuclei of the thalamus. Further rostrally, terminal labelling was particularly evident in the ipsilateral pallidal complex, especially in the caudal two-thirds of the entopeduncular nucleus and the ventral half of the caudal third of the globus pallidus. Caudal to pedunculopontine injection sites dense labelling was observed in the reticular formation of the pontine tegmentum. In a final series of experiments, confirmation of apparent pedunculopontine efferent projections was sought using the retrograde transport of horseradish peroxidase. Enzyme was injected into sites possibly receiving pedunculopontine efferents and the peribrachial area of the brain stem was examined for retrograde cell labelling. In this way, pedunculopontine projections were confirmed to the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra, parafascicular nucleus and pontine reticular formation. Injections into the globus pallidus or subthalamic nucleus gave rise to retrograde cell labelling bilaterally in pedunculopontinus. In addition, retrograde transport studies alone demonstrated projections from pedunculopontinus to the cerebral cortex and to the spinal cord. It is concluded that the nucleus tegmenti pedunculopontinus has reciprocal relationships with parts of the basal ganglia and some functionally related nuclei (in particular, the pallidal complex, subthalamic nucleus and substantia nigra).(ABSTRACT TRUNCATED AT 400 WORDS)