Inhibitory postsynaptic potentials (IPSPs) in neocortical pyramidal neurons are increased in duration and amplitude at depolarized membrane potentials. This effect was not due to changes in the time course of the underlying synaptic current. The role of postsynaptic voltage-activated channels was investigated by mimicking the voltage change that occurs during an IPSP with current injections. The peak and integral of these 'simulated' IPSPs increased during depolarization of the membrane potential in a tetrodotoxin-sensitive manner. This amplification presumably occurs as the hyperpolarization associated with IPSPs turns off sodium channels that are tonically active at depolarized membrane potentials. IPSP amplification increased the ability of IPSPs to inhibit action potential firing and promoted IPSP-induced action potential synchronization.