Deprivation-induced plasticity of sensory cortical maps involves long-term potentiation (LTP) and depression (LTD) of cortical synapses, but how sensory deprivation triggers LTP and LTD in vivo is unknown. Here we tested whether spike timing-dependent forms of LTP and LTD are involved in this process. We measured spike trains from neurons in layer 4 (L4) and layers 2 and 3 (L2/3) of rat somatosensory cortex before and after acute whisker deprivation, a manipulation that induces whisker map plasticity involving LTD at L4-to-L2/3 (L4-L2/3) synapses. Whisker deprivation caused an immediate reversal of firing order for most L4 and L2/3 neurons and a substantial decorrelation of spike trains, changes known to drive timing-dependent LTD at L4-L2/3 synapses in vitro. In contrast, spike rate changed only modestly. Thus, whisker deprivation is likely to drive map plasticity by spike timing-dependent mechanisms.