The regional distribution of high affinity binding sites for kainic acid has been determined in rat hippocampi by quantitative autoradiography. Selective lesions were made in order to determine the exact localization of these sites in the mossy fiber system, and to evaluate whether the sprouting and synaptic reorganization of the mossy fibers are associated with alterations in the distribution of these binding sites. The results show that kainate binding sites in the stratum lucidum are more vulnerable to destruction of the granules and their mossy fibers by intrahippocampal colchicine injections than to destruction of the CA3/CA4 pyramidal cells by injection of kainate into the amygdala. This suggests that a substantial proportion of the kainate binding sites is associated with the mossy fiber terminals (i.e. the presynaptic elements). Furthermore, in keeping with an earlier study, destruction of the pyramidal neurons of CA3 by intracerebral kainate produced a dark Timm positive band in the supragranular zone which is due to the sprouting of mossy fibers. This was associated with an increase in the density of kainate binding sites, which further stresses the parallelism between the distribution of these sites and mossy fiber terminals.