Studies of the mechanisms of epileptogenesis in brain-slice model systems have emphasized the role of three interacting processes in the development of interictal discharge. These processes are intrinsic burst activity, disinhibition, and excitatory synaptic coupling. Intrinsic membrane excitability may be altered by neuromodulators, injury, genetic mutations, and other factors. Disinhibition releases intrinsic burst-generating capacities in subpopulations of neurons and may become an important factor following cortical injury or repetitive activation of inhibitory circuits. Excitatory synaptic coupling is required in order to synchronize populations of neurons. Synaptic currents also serve as a major generator of slow depolarization shifts in individual neurons. The contribution of each of these factors to epileptogenesis may vary with the type of pathological process and the properties of the specific neuronal population.