In vivo whole-cell recordings revealed that during repeated stimulation, synaptic responses to deflection of facial whiskers rapidly adapt. Extracellular recordings in the somatosensory thalamus revealed that part of the adaptation occurs subcortically, but because cortical adaptation is stronger and recovers more slowly, cortical mechanisms must also contribute. Trains of sensory stimuli that produce profound sensory adaptation did not alter intrinsic membrane properties, including resting membrane potential, input resistance, and current-evoked firing. Synaptic input evoked via intracortical stimulation was also unchanged; however, synaptic input from the somatosensory thalamus was depressed by sensory stimulation, and this depression recovered with a time course matching that of the recovery of sensory responsiveness. These data strongly suggest that synaptic depression of thalamic input to the cortex contributes to the dynamic regulation of neuronal sensitivity during rapid changes in sensory input.