Objective: Synaptic vesicle recycling has been proposed to depend on proteins which coordinate membrane and cytoskeletal dynamics. We have examined the role of the dynamin- and N-WASP-binding protein syndapin/PACSIN at the lamprey reticulospinal synapse. Methods: Presynaptic microinjections was combined with imaging, electrophysiology and electron microscopy. Results: We find that presynaptic microinjection of syndapin antibodies inhibits vesicle recycling evoked by intense (5 Hz or more), but not by light (0.2 Hz) stimulation. This contrasts with the marked inhibition at light stimulation induced by perturbation of e.g. dynamin-amphiphysin interactions. Inhibition by syndapin antibodies was associated with massive accumulation of membranous cisternae and invaginations around release sites, but not of coated pits at the plasma membrane. Cisternae contained vesicle membrane, as shown by VAMP2/synaptobrevin 2 immunolabeling. Similar effects were observed when syndapin was perturbed before onset of a single round of massive endocytosis induced by preceding intense stimulation. Selective perturbation of the SH3 domain interactions of syndapin using Fab fragments was sufficient to induce vesicle depletion and accumulation of cisternae. Conclusion: We did not detect direct involvement of syndapin in clathrin-mediated synaptic vesicle endocytosis. Our data show, however, that syndapin is critical to maintain the organization of the plasma membrane of the periactive zone during periods of high vesicle membrane turnover. This function may involve participation in bulk endocytosis.