The functions of prefrontal cortex (PFC) areas are constrained by their anatomical connections. There is little quantitative information about human PFC connections, and, instead, our knowledge of primate PFC connections is derived from tracing studies in macaques. The connections of subcortical areas, in which white matter penetration and hence diffusion anisotropy are greatest, can be studied with diffusion-weighted imaging (DWI) tractography. We therefore used DWI tractography in four macaque and 10 human hemispheres to compare the connections of PFC regions with nine subcortical regions, including several fascicles and several subcortical nuclei. A distinct connection pattern was identified for each PFC and each subcortical region. Because some of the fascicles contained connections with posterior cortical areas, it was also possible to draw inferences about PFC connection patterns with posterior cortical areas. Notably, it was possible to identify similar circuits centered on comparable PFC regions in both species; PFC regions probably engage in similar patterns of regionally specific functional interaction with other brain areas in both species. In the case of one area traditionally assigned to the human PFC, the pars opercularis, the distribution of connections was not reminiscent of any macaque PFC region but, instead, resembled the pattern for macaque ventral premotor area. Some limitations to the DWI approach were apparent; the high diffusion anisotropy in the corpus callosum made it difficult to compare connection probability values in the adjacent cingulate region.