Changes in the granule cells of the rat dentate gyrus, hippocampal mossy fibers and moosy fiber boutons following administration of picrotoxin were examined at the ultrastructual level. In controls, many small round clear vesicles (20-40 nm in diameter) along with a small number of large dense-core vesicles (60-90 nm in diameter) filled the mossy fiber boutons. Following administration of picrotoxin, the large dense-core vesicles increased in number and accumulated on the presynaptic membrane. Some of the large dense-core vesicles appeared to be fused with the membrane and frequently exhibited omega-shaped exocytotic profiles. A greatly increased number of coated vesicles (60-90 nm in diameter) was observed on the maturing face of the Golgi fields in the cytoplasm of granule cells after injection of picrotoxin. In addition, the ends of the Golgi cisternae rods occasionally appeared to be coated, and coated large dense-core vesicles (60-80 nm in diameter) were seen in the mossy fibers. This study showed not only an increased incidence of large dense-core vesicle exocytosis during seizures, but also suggests that these vesicles are replaced in excess from the perikaryon.