The orbital and medial prefrontal cortex (OMPFC) of macaque monkeys is a large but little understood region of the cerebral cortex. In this study the architectonic structure of the OMPFC was analyzed with nine histochemical and immunohistochemical stains in 32 individuals of three macaque species. The stains included Nissl, myelin, acetylcholinesterase, Timm, and selenide stains and immunohistochemical stains for parvalbumin, calbindin, a nonphosphorylated neurofilament epitope (with the SMI-32 antibody), and a membrane-bound glycoprotein (with the 8b3 antibody). In addition to patterns of cell bodies and myelinated fibers, these techniques allow the visualization of markers related to metabolism, synapses, and neurotransmitters. A cortical area was defined as distinct if it was differentiated in at least three different stains and, as described in later papers, possessed a distinct set of connections. Twenty-two areas were recognized in the OMPFC. Walker's areas 10, 11, 12, 13, and 14 [J. Comp. Neurol. (1940) 73:59-86] have been subdivided into areas 10m, 10o, 11m, 11l, 12r, 12l, 12m, 12o, 13m, 13l, 13a, 13b, 14r, and 14c. On the medial wall, areas 32, 25, and 24a,b,c have been delineated, in addition to area 10m. The agranular insula also has been recognized to extend onto the posterior orbital surface and has been subdivided into medial, intermediate, lateral, posteromedial, and posterolateral agranular insula areas. The OMPFC, therefore, resembles other areas of primate cortex, such as the posterior parietal and temporal cortices, where a large number of relatively small, structurally and connectionally distinct areas have been recognized. Just as the area-specific neurophysiological properties of these parietotemporal areas underlie broader regional functions such as visuospatial analysis, it is likely that the many small areas of the OMPFC also make differential contributions to the general mnemonic, sensory, and affective functions of this region.