The corticothalamic projections to the prefrontal cortex have been shown to be topographically organized. However, the underlying basis for this topography as it relates to the organization of the different architectonically defined areas of the prefrontal cortex has not been systematically studied. In the present investigation we have reassessed the thalamic projections from the different architectonic areas of the prefrontal cortex by using the technique of autoradiography in the rhesus monkey. The results show that the prefronto-mediodorsal projections are organized according to the architectonic differentiation of the prefrontal cortices. Thus architectonically less differentiated medial and orbital prefrontal regions project to the medial sector of the mediodorsal nucleus, the magnocellular subdivision. In contrast, highly differentiated prefrontal area 8 projects to the most lateral sector of the mediodorsal nucleus, the multiformis subdivision. Lateral prefrontal areas with intermediate architectonic features project to the central parvocellular sector of the mediodorsal nucleus. Additionally, these projections also reveal a dorsoventral topography. Thus areas in the medial and dorsolateral cortices project to the dorsal part of the mediodorsal nucleus. In contrast, areas in orbital and ventrolateral cortices project to the ventral part of the mediodorsal nucleus. The topographic organization of the corticothalamic connections described in this study corresponds to the progressive elaboration and differentiation of the architectonic features of the different prefrontal areas. This successive and dichotomous organization of prefrontothalamic connections may provide the basis for the observed differential functions of the prefrontal cortex and the mediodorsal nucleus.