Cortical map plasticity is thought to involve long-term depression (LTD) of cortical synapses, but direct evidence for LTD during plasticity or learning in vivo is lacking. One putative role for LTD is in the reduction of cortical responsiveness to behaviorally irrelevant or unused sensory stimuli, a common feature of map plasticity. Here we show that whisker deprivation, a manipulation that drives map plasticity in rat somatosensory cortex (S1), induces detectable LTD-like depression at intracortical excitatory synapses between cortical layer 4 (L4) and L2/3 pyramidal neurons. This synaptic depression occluded further LTD, enhanced LTP, was column specific, and was driven in part by competition between active and inactive whiskers. The synaptic locus of LTD and these properties suggest that LTD underlies the reduction of cortical responses to deprived whiskers, a major component of S1 map plasticity.