Heterotopic transplantation analysis suggests that individual areas of the developing neocortex have the capacity to differentiate many of the architectural and connectional features normally characteristic of other neocortical areas. Many studies indicate a pivotal role for thalamocortical afferents in the differentiation of the area-specific features that distinguish neocortical areas. Both activity-dependent and activity-independent mechanisms contribute to the patterning of thalamocortical afferent terminations. The available evidence suggests that positional information is established in the cortical subplate and that this information controls the precise targeting of developing thalamocortical axons. In this way appropriate thalamocortical relationships can be established that allow these afferents to promote the differentiation of the functionally specialized and anatomically distinct areas of the adult neocortex.