The projection of the substantia nigra-ventral tegmental area (SN-VTA) to the ipsilateral and contralateral caudate-putamen was studied with double-labeling fluorescence techniques in the albino rat. By combining glyoxylic acid histofluorescence with retrograde fluorescence tracers, we were able to determine that 93% of the minor (1-2%) contralateral mesostriatal pathway is catecholaminergic. In addition, combined immunofluorescence and retrograde fluorescence tracer studies showed that 50% of the crossed mesostriatal pathway also arises from cholecystokinin-containing neurons. These results provide evidence for crossed catecholamine- and peptide-containing pathways in the mesostriatal system which is part of the 'prefrontal system' that links the prefrontal cortex through the caudate-putamen, with the thalamus and tectum of each hemisphere.