Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.