Pyramidal neurons in layer VI of striate cortex are the source of descending projections to the lateral geniculate nucleus (LGN) as well as a major source of axon terminals in the layers of striate cortex that receive LGN projections. This study examines how the connections of layer VI neurons are arranged with respect to the functionally distinct classes of neurons that compose their cortical and subcortical targets. By placing injections of biocytin into layer VI of tree shrew striate cortex, we identified two sublayers that differ in their intracortical and thalamic connections. Neurons in the upper part of layer VI, layer VIa, terminate in cortical layer IV, whereas those in the lower part of layer VI, layer VIb, terminate throughout the supragranular layers, layers I-III. The selectivity of layer VI subdivisions for the granular and supragranular layers is also evident in their descending projections. Neurons in layer VIa terminate preferentially in the LGN layers that supply layer IV (LGN layers 1, 2, 4, and 5), whereas neurons in layer VIb terminate in the LGN layers that supply layers I-III (LGN layers 3 and 6) and in the pulvinar nucleus. Additional subclasses of layer VIa neurons were identified based on the restriction of their terminal fields to narrow subtiers within layer IV. By influencing the activity of distinct populations of cortical neurons and the thalamic neurons that supply them, layer VI neurons could exert a powerful influence on the flow of activity in functionally distinct cortical circuits.