The adult cerebral cortex extends axons to a variety of subcortical targets, including the thalamus and superior colliculus. These descending projections are pioneered during development by the axons of a transient population of subplate neurons (McConnell et al., 1989). We show here that the descending axons of cortical plate neurons appear to be delayed significantly in their outgrowth, compared with those of subplate neurons. To assess the possible role of subplate neurons in the formation of these pathways, subplate neurons were ablated during the embryonic period. In all cases, an axon pathway formed from visual cortex through the internal capsule and into the thalamus. In half of all cases, however, cortical axons failed to invade their normal subcortical targets. In the other half, targets were innervated normally. Subplate neurons are therefore likely to provide important cues that aid the process by which cortical axons grow toward, select, and invade their subcortical targets.