The mechanisms underlying experience-dependent plasticity and refinement of central circuits are not yet fully understood. A non-Hebbian form of synaptic plasticity, which scales synaptic strengths up or down to stabilize firing rates, has recently been discovered in cultured neuronal networks. Here we demonstrate the existence of a similar mechanism in the intact rodent visual cortex. The frequency of miniature excitatory postsynaptic currents (mEPSCs) in principal neurons increased steeply between post-natal days 12 and 23. There was a concomitant decrease in mEPSC amplitude, which was prevented by rearing rats in complete darkness from 12 days of age. In addition, as little as two days of monocular deprivation scaled up mEPSC amplitude in a layer- and age-dependent manner. These data indicate that mEPSC amplitudes can be globally scaled up or down as a function of development and sensory experience, and suggest that synaptic scaling may be involved in the activity-dependent refinement of cortical connectivity.