In rodents, somatosensory cortex receives input primarily from the contralateral whiskers, but cortico-cortical connections also provide input from ipsilateral whiskers. Although direct connections between callosal afferents and cortical neurons are glutamatergic, the net effect of this input is thought to be inhibitory, resulting in reduced receptive field size. In these studies, we examined the role that evoked sensory activity from ipsilateral whiskers has on plasticity induced by single-whisker experience (SWE) using single unit recording in vivo. Anaesthesia was induced with isoflurane and maintained with i.p. injections of urethane (1.5g/kg whole body weight). Level of anesthesia was monitored by recording focal EEG activity, spontaneous cortical spike activity, breathing rate, and reflexes. In this experimental protocol, where all but a single whisker from one side of the rodent face had been removed, neuronal responses to stimulation of the spared whisker increase and responses to stimulation of previously deprived whiskers decrease. By comparing expansion of the spared whisker representation in the presence and absence of ipsilateral whiskers (SWE-unilateral and SWE-bilateral), we examined whether these manipulations could influence plasticity. This experimental paradigm is similar to forced-use therapy, an effective rehabilitative therapy primarily used to restore motor function in people. Neuronal responses to whisker deflection after 16-20 days of deprivation (SWE-unilateral or SWE-bilateral) followed by 6-10 days of whisker regrowth were recorded in supragranular layers of primary somatosensory cortex and quantified as the number of spikes per stimulus. Results indicate that plasticity of the spared whisker after bilateral deprivations is doubled compared to unilaterally deprived animals. This is due to an increase in the spared whisker responses in the spared barrel column (2.69±0.46 spikes per stimulus for SWE-bilateral versus 1.31±0.26 spikes per stimulus for SWE-unilateral; p<0.05) as well as surrounding barrel columns (1.69±0.11 spikes per stimulus for SWE-bilateral versus 0.89±0.12 spikes per stimulus for SWE-unilateral; p<0.05). Bilateral deprivation did not change depression of deprived whisker responses. These data are consistent with a model in which silencing of callosal projections from contralateral cortex increases receptive field size, providing an increased neural substrate for plastic changes around the spared whisker representation. Furthermore, these results indicate that mechanisms facilitating plasticity during forced-use therapy in motor cortex may generalize to sensory cortex.