Summary Cultures of mouse cerebellum were exposed for various intervals after explantation to kainic acid, a glutamic acid analog. Purkinje cells and intracerebellar nucleus neurons were destroyed and cortical laminar formation was inhibited by exposure to kainic acid, while granule cells were relatively spared. Prolonged kainate treatment also reduced the granule cell population. The destructive effects of kainic acid were evident upon exposure of Purkinje cells prior to the development of parallel fiber-Purkinje cell synapses, the neurotransmitter for which is believed to be glutamic acid. Glutamate application to intracerebellar nucleus neurons in vitro did not evoke extracellularly recorded excitatory effects, suggesting that these kainate-sensitive neurons do not have significant numbers of glutamate receptors. The combination of these observations suggests that neuronal toxic effects of kainic acid are not exclusively mediated by action on glutamate receptors, but involve other, less specific mechanisms as well.