In many common experimental conditions the majority of the neurons isolated in cat and rat somatosensory cortex using extracellular recording techniques are unresponsive to somatic stimuli. This population of cells becomes amenable to experimental manipulation with iontophoretic administration of glutamate, other putative neurotransmitters, and their agonists and antagonists. During administration of glutamate or bicuculline methiodide as many as half of the unresponsive cells could be shown to receive somatic inputs that did not drive the cells without drug treatments. Several hypotheses are discussed concerning the possible origin and function of the unresponsive neurons and the conditions under which they might play an active role in cortical function such as during altered patterns of afferent input, enhanced release of acetylcholine, reduction of GABAergic inhibition and situations involving learning or directed attention. The unresponsive neurons may be a characteristic that differentiates somatosensory cortex from subcortical sensory pathways.