The callosal projections of the cerebral cortex play an important role in the functional integration of the two hemispheres, and the anatomy of these connections has been extensively studied in primary sensory and motor regions. In the present investigation, we examined the synaptic targets of callosal terminals in a limbic association area, the prefrontal cortex (PFC) in the rat. In addition, we examined the relationship of callosal afferents to GABA local circuit neurons within the PFC. Callosal terminals were labeled by either anterograde transport of Phaseolus vulgaris leucoagglutinin from superficial or deep layers or by anterograde degeneration following electrolytic lesion of the contralateral PFC. Callosal terminals in either the superficial or deep layers labeled by either method formed primarily asymmetric axo-spinous synapses (approximately 95%), while the remainder formed axo-dendritic synapses. Some of the dendrites postsynaptic to callosal terminals exhibited a morphology characteristic of local circuit neurons. This observation was confirmed in tissue immunolabeled for GABA, in which degenerating callosal terminals sometimes formed asymmetric synapses on GABA-labeled dendrites. In addition, GABA-labeled terminals and callosal afferents were sometimes observed to converge onto common postsynaptic dendritic shafts or spines within the PFC. These results indicate that callosal terminals in limbic association cortex, consistent with sensory and motor cortices, primarily target the spines of pyramidal neurons. In addition, the results suggest that callosal afferents to the PFC interact with GABA local circuit neurons at multiple levels. Specifically, a proportion of callosal terminals appear to provide excitatory drive to GABA cells, while GABA terminals may modulate the excitation from callosal inputs to the distal dendrites and spines of PFC pyramidal neurons.