The retrograde, horseradish peroxidase technique has been used to demonstrate the cells of origin of corticofugal fiber systems arising in the rat somatic sensory cortex and projecting to the striatum, diencephalon, brainstem, and spinal cord. Correlative experiments conducted with the anterograde, autoradiographic method have been used to confirm the terminal distribution of many of these fiber systems. Corticofugal pathways directed to subcortical structures arise in the first and second somatic sensory areas exclusively from pyramidal cells of the infragranular layers, V and VI. Fibers which descend to the midbrain, pons, medulla and spinal cord arise exclusively from the largest pyramidal cells, the somata of which are found in the deep part of layer V (layer VB). There is some evidence for a sublaminar organization of the different classes of efferent cells within this layer. Fibers projecting to the diencephalon arise from somata situated throughout layer VI and to a lesser extent in layer V. Corticostriatal fibers arise only from cells with somata in layer V, but the somata are more superficially situated than those of the other classes of corticofugal neurons. The laminar distribution of the somata of corticofugal neurons differs considerably from that of commissural and ipsilateral corticocortical neurons.