Septins are GTPases required for the completion of cytokinesis in diverse organisms, yet their roles in cytokinesis or other cellular processes remain unknown. Here we describe studies of a newly identified septin, CDCrel-1, which is predominantly expressed in the nervous system. This protein was associated with membrane fractions, and a significant fraction of the protein copurified and coprecipitated with synaptic vesicles. In detergent extracts, CDCrel-1 and another septin, Nedd5, immunoprecipitated with the SNARE protein syntaxin by directly binding to syntaxin via the SNARE interaction domain. Transfection of HIT-T15 cells with wild-type CDCrel-1 inhibited secretion, whereas GTPase dominant-negative mutants enhanced secretion. These data suggest that septins may regulate vesicle dynamics through interactions with syntaxin.