Cortical spreading depression (SD) represents a pathophysiological signal that has been associated with the induction of migraine and ischaemic brain damage. The properties of repetitive SDs and their effects on excitatory and inhibitory synaptic transmission were analysed in neocortical slices obtained from adult rats. The SD showed only small variations in amplitude, duration and integral when elicited four times at intervals of 30 min. Extracellularly recorded paired pulse inhibition was, however, significantly reduced by approximately 10% with each SD episode. Since excitatory synaptic transmission was unaffected, our data indicate that repetitive SD causes a selective reduction of intracortical inhibition.