The morphological and functional consequences of epileptic activity were investigated by applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures. After 3 days, some cells in all hippocampal subfields showed signs of degeneration, including swollen somata, vacuolation, and dendritic deformities, whereas others displayed only a massive reduction in the number of their dendritic spines. Intracellular recordings from CA3 pyramidal cells revealed a decrease in the amplitude of evoked excitatory synaptic potentials. gamma-Aminobutyric acid-releasing interneurons and inhibitory synaptic potentials were unaffected. Seven days after withdrawal of convulsants, remaining cells possessed a normal number of dendritic spines, thus demonstrating a considerable capacity for recovery. The pathological changes induced by convulsants are similar to those found in the hippocampi of human epileptics, suggesting that they are a consequence, rather than a cause, of epilepsy.