Unilateral injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in the internal segment of the pallidum (GPi) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers ipsilaterally in the following thalamic nuclei: ventral anterior (VA), ventral lateral (VL), centromedian (CM), and lateral habenula (Hbl). The labeled fibers reached these ipsilateral thalamic nuclei by coursing along or through the ansa lenticularis, the lenticular and thalamic fasciculi, and the Forel's fields. They arborized profusely in VA/VL nuclei where they displayed small glomerule-like formations. Numerous labeled fibers also occurred in the CM. Most of them were long, varicose and gave rise to shorter fibers that formed a dense terminal field covering a large portion of the CM. A small but dense terminal field composed of delicate fibers and extremely fine terminals was noted in the Hbl. A large contingent of labeled fibers were seen to cross the midline, principally at the rostral pole of the CM and in the supramammillary decussation, to reach the contralateral thalamus where they arborized profusely in the VA/VL and CM nuclei, but not in the Hbl. The patterns of termination of these contralateral pallidothalamic fibers were strikingly similar to those observed ipsilaterally. Other anterogradely labeled fibers were also noted bilaterally in the pedunculopontine nucleus (TPP) and ipsilaterally in the external segment of the pallidum (GPe) and in the putamen. Complementary, double-labeling, retrograde studies involving the injection of nuclear yellow in the VA/VL and CM nuclei and Fast blue in the TPP, confirmed the existence of contralateral pallidothalamic and pallidotegmental projections. The number of retrogradely labeled cells in the contralateral GPi amounted approximately to 10-20% that in the ipsilateral GPi. These experiments further indicated that contralaterally projecting pallidothalamic neurons exhibited a high degree of axonal collateralization, the majority of its neurons projecting also to the contralateral TPP. Cells retrogradely labeled with the tracer injected into the thalamus were also encountered bilaterally in the thalamic reticular nucleus. Taken together, the results of these anterograde and retrograde investigations indicate that the contralateral pallidothalamic projection involves a relatively small population of GPi neurons, but that these neurons arborize extensively in their contralateral thalamic targets. Furthermore, the presence of retrogradely labeled cells in the ipsi- and contralateral reticular thalamic nucleus indicates that the VA/VL and CM nuclei, which receive a massive input from the GPi, are under the bilateral influence of this perithalamic nucleus. Such contralateral projections could play a major role in the subcortical organization of the bilateral aspect of normal basal ganglia function.(ABSTRACT TRUNCATED AT 400 WORDS)