The nigrothalamocortical connections and their topography were analyzed by autoradiography and double or triple retrograde labeling with the fluorescent dyes Fast Blue, Diamidino Yellow, and Propidium Iodide. Injections of tritiated leucine into different parts of the substantia nigra (SN) revealed that the medial SN projects to the medial magnocellular subdivisions of the ventral anterior (VAmc) and mediodorsal (MDmc) nuclei of the thalamus while the lateral SN projects to the more lateral and more posterior part of the VAmc, and the paralaminar, parvicellular, and densocellular subdivisions of the mediodorsal nucleus (MDmf, MDpc, and MDdc). With the exception of the MDmf, terminal areas observed in the mediodorsal nucleus were in the form of scattered clusters of grains. Analysis of the thalamus in cases with fluorescent dye injections into the lateral orbital gyrus (Walker's area 11), principal sulcus (area 46), anterior bank of the arcuate gyrus (areas 8 and 45), supplementary motor area (area 6), and motor cortex (area 4) revealed topographic organization of the nigrothalamocortical projection system. The parts of the VAmc and MDmc which receive afferents from the medial part of the SN in turn project to the most anterior regions of the frontal lobe including principal sulcus and orbital cortex. The lateral posterior VAmc, MDmf, MDpc, and MDdc, all of which receive afferents from the lateral part of the SN; project to more posterior regions of the frontal lobe including, in addition to the principal sulcus, the frontal eye field and also areas of the premotor cortex. These findings indicate that the SN has preferential targets in the thalamus and cerebral cortex which are segregated from those of the globus pallidus and cerebellum. Whereas the motor cortex is the primary target of cerebellar output (Asanuma et al., '83b), and the premotor cortex is the target of pallidal output (Schell and Strick, '84), the SN output appears to be directed more anteriorally--to the prefrontal cortex.