In macaque monkeys with injections of tritiated amino acids or horseradish peroxidase in the ventrolateral granular frontal cortex, we observed extensive anterograde and retrograde labeling of the premotor and somatosensory cortex in and around the lateral sulcus. Comparable labeling was not present with large and small control injections of the dorsal granular cortex. Cytoarchitectonic evaluation of the perisylvian cortex in the three cases examined in detail indicated that labeled areas included the ventral premotor cortex (area 6V); the precentral opercular and orbitofrontal opercular areas (PrCO and OFO); the second somatosensory area (S-II); the opercular cortex immediately anterior to S-II, possibly corresponding to area 2 of the S-I complex; and the central part of the insular cortex, including portions of the granular and dysgranular insular fields (Ig, Idg). Labeling was particularly dense and extensive in areas 6V, S-II, and OFO. Lighter labeling was also present in the rostral inferior parietal lobule (areas 7b and POa). The distribution of label within perisylvian areas was not uniform: certain parts were heavily labeled, while other parts were lightly labeled or unlabeled. Comparison of label distribution with published accounts of the somatotopy of these areas indicates that forelimb and orofacial representations were selectively labeled. Further, our results, taken together with other recent anatomical findings (e.g., Matelli et al.: Journal of Comparative Neurology 251:281-298, 1987; Barbas and Pandya: Journal of Comparative Neurology 256:211-228, 1987) suggest strongly that there is a network of interconnected forelimb and orofacial representations in macaque cortex, involving the ventral granular frontal cortex, area 6V, OFO, opercular area 2, S-II, the central insula, and area 7b. Each injection of frontal cortex which labeled the perisylvian somatic cortex involved the cortex of the ventral rim of the principal sulcus (PSvr). The cortex surrounding the PSvr does not stand out as a distinct area in Nissl-stained material. However, examination of myelin-stained sections prepared from uninjected hemispheres with the Gallyas technique revealed the existence of a distinct zone centered on the PSvr. This myeloarchitectonic area, which we term area 46vr, is more heavily myelinated than the ventral bank and fundus of the principal sulcus (area 46v) but is less heavily myelinated than the ventral (inferior) convexity (area 12). Involvement of area 46vr in our injections was probably responsible for the strong labeling observed in perisylvian somatic areas.(ABSTRACT TRUNCATED AT 400 WORDS)