The afferent and efferent connections of the vibrissal representation within the mouse primary motor cortex (MsI) were identified by using the retrograde transport of horseradish peroxidase (HRP) and the anterograde transport of tritiated amino acids injected into MsI. Following aldehyde perfusion brains were frozen-sectioned at 40 microns and reacted for HRP using the 3-3' diaminobenzidine-cobalt chloride technique of Adams ('77). Alternate HRP reacted sections were processed for autoradiography. HRP-filled pyramidal cell somata and concentrations of developed silver grains above background levels were observed in both the vibrissal area of primary somatosensory cortex (SmI) cortex (i.e., the posteromedial barrel subfield; PMBSF cortex) and in the face region of SmII (area 40). In both regions labeled somata occurred predominantly in cortical layers II-III and V. Autoradiographic label was superimposed over the regions containing labeled somata but exhibited a less distinct laminar organization. A dense reciprocal projection connected the injection site with the homotopic area in contralateral MsI; somata occurred for the most part in layers III and V. Developed silver grains were uniformly dispersed over the area containing labeled cell bodies. HRP-labeled pyramidal somata were noted in contralateral PMBSF cortex, but no silver grains occurred in this region. Reciprocal projections linked MsI cortex with the ipsilateral thalamic nuclei: ventralis pars lateralis (VL) and centralis pars lateralis (CL) and with the zona incerta (ZI). Labeled cell bodies and developed silver grains were more dense in VL than in CL. The ipsilateral striatum and thalamic reticular nucleus (NRT) received afferents from the motor cortex but did not project to it. Thus, the vibrissal area of primary motor cortex is connected with a number of cortical and subcortical structures, each of which has been shown to play a role in motor performance. Identification of the afferent and efferent pathways of MsI cortex will now enable further investigation of the ultrastructural and synaptic organization of the vibrissal area of MsI.