The hippocampus contains three times as much dynorphin-17 immunoreactivity (ir) as enkephalin-ir. Hippocampal mossy fibers exhibit weak enkephalin and strong dynorphin immunostaining. Intrahippocampal colchicine injections, which selectively destroy dentate granule cells, reduce enkephalin-ir and dynorphin-ir in mossy fibers. Intraventricular kainic acid, which causes degeneration of CA3-4 pyramidal cells, results in increased enkephalin immunostaining in mossy fibers. The enkephalin-ir cells and fibers of the entorhinal cortex which innervate the hippocampus and dentate gyrus do not contain dynorphin-ir.