The inhibitory circuitry of the ventroposterolateral nucleus (VPL) of the macaque somatosensory thalamus was analyzed in normal animals and in those surviving for a few days or several weeks following a unilateral lesion of the cuneate nucleus, the source of medial lemniscal (ML) axons carrying information from the contralateral upper extremity. Inhibitory synaptic terminals in the VPL were defined as those that contain flattened or pleomorphic synaptic vesicles and that can be shown to be immunoreactive for gamma-aminobutyric acid (GABA). There are two types of these profiles: F axon terminals that arise from neurons of the thalamic reticular nucleus, and perhaps from VPL local circuit neurons (LCNs); and the dendritic appendages of LCNs that form presynaptic dendrites (PSDs). ML terminals normally have extensive synaptic interactions with PSDs but not with F axon terminals. Electron microscopic analyses revealed that cuneatus lesions resulted in a rapid loss of ML terminals and a statistically significant reduction in both F and PSD synaptic profiles. Confocal scanning microscopy also demonstrated a profound loss of GABA immunoreactivity in the deafferented VPL. These changes persisted for more than 20 weeks, without any evidence of reactive synaptogenesis of surviving sensory afferents or of inhibitory synapses. The changes in GABA circuitry are transneuronal, and the possible mechanisms that may underlie them are discussed. It is suggested that the altered GABAergic circuitry of the VPL in the monkey may serve as a model for understanding changes in somatic sensation in the human following peripheral or central deafferentation.