The morphological effects of repetitive neuronal activation following systemic kainic acid administration were examined in hippocampal CA1 stratum radiatum synapses. Sporadic activation of CA3 and CA1 neurons began approximately 15-25 min after kainic acid administration, which was followed at 1-2 h by repetitive ictal firing until the completion of the experiments at 4 hr. Synaptic density in the CA1 region increased following stimulation, reaching significance at the earliest time period examined, approximately 5-15 min postactivation. There was an initial increase and then a decline in frown (and then flat)-shaped synaptic subtypes, with an ultimate increase in smile-shaped synapses. This pattern is consistent with either a change in synapses from frown to smile shaped or a selective gain/loss of synaptic subtypes. There was also an increase in the size of smile-shaped synapses, but a decrease in the size of frown synapses. By 4 h there was a decline in most indices of synaptic morphology, suggesting that the stimulation had become cytotoxic. These results indicate that the number and morphology of synapses and synaptic subtypes can be modified with relatively short periods of repeated use and suggest their potential role in activity-dependent phenomenon such as information storage and epilepsy.