The strength of the connection between two neurons can be modified by activity, in a way that depends on the timing of neuronal firing on either side of the synapse. This spike-timing-dependent plasticity (STDP) has been studied by systematically varying the intervals between pre- and postsynaptic spikes. Here we studied how STDP operates in the context of more natural spike trains. We found that in visual cortical slices the contribution of each pre-/postsynaptic spike pair to synaptic modification depends not only on the interval between the pair, but also on the timing of preceding spikes. The efficacy of each spike in synaptic modification was suppressed by the preceding spike in the same neuron, occurring within several tens of milliseconds. The direction and magnitude of synaptic modifications induced by spike patterns recorded in vivo in response to natural visual stimuli were well predicted by incorporating the suppressive inter-spike interaction within each neuron. Thus, activity-induced synaptic modification depends not only on the relative spike timing between the neurons, but also on the spiking pattern within each neuron. For natural spike trains, the timing of the first spike in each burst is dominant in synaptic modification.