A number of studies have shown that sensory deprivation is associated with selective decreases in GABA, GAD, and GABA receptors, in deprived areas of visual and somatosensory cortex. Those studies focused on layer 4, a recipient of direct thalamocortical sensory input. However, supragranular layers 2/3 have been recently identified as a major locus of functional plasticity in sensory deprivation and long-term potentiation. To examine whether GABAA receptors in layers 2/3 are affected by sensory deprivation, rats had mystacial vibrissae in middle row C or rows ABDE trimmed for 6 weeks beginning in early adulthood. Layers 2/3 above the deprived and adjacent whisker barrels were located in tangential sections, using patterns of radial blood vessels as fiducial marks. In deprived whisker barrel columns, [3H]muscimol binding to GABAA receptors decreased by 12.8% ± 1.2 (P &lt; 0.001) in layers 2/3 and 11.4% ± 1.2 (P<0.001) in layer 4. Altered levels of GABAA α1 subunit (Fritschy et al., 1994) were indicated by reduced optical density of immunostaining, both in deprived layers 2/3 (6.4% ± 0.7; P&lt; 0.001) and in layer 4 (3.4% ± 1.0; P &lt; 0.005). Interestingly, Nissl staining density also decreased in deprived layers 2/3 (12.7% ± 1.8 P &lt; 0.001) and in 4 (6.0 ± 0.7 (P &lt; 0.001). The percent decreases were greater in layers 2/3 than in 4 for both GABAA α1 (P &lt; 0.05) and Nissl substance (P &lt; 0.005). The present results suggest that down-regulation in GABAA receptors may underlie the physiological signs of disinhibition observed in neurons of layer 2/3 and 4 in deprived whisker barrel columns.