The SNARE hypothesis proposes that specificity of exocytosis is regulated by the appropriate interactions between the vesicle (v-) SNARE and the target membrane (t-) SNAREs. We show here that pancreatic acinar cells express the SNAP-25 t-SNARE homolog SNAP-23, and find that this t-SNARE is most highly concentrated on the basolateral plasma membrane while being expressed below detectable levels in endocrine islets within the same tissue. This is the first localization of SNAP-23 within a polarized tissue and suggests that this t-SNAREs may interact with syntaxin-4 to mediate basolateral secretion.