Calcium-dependent activator protein for secretion (CAPS) was initially identified in brain cytosol based on its ability to reconstitute calcium-triggered dense-core vesicle (DCV) exocytosis in permeable cell lines (PC12) of adrenal chromaffin origin. Current evidence indicates that CAPS functions selectively in DCV exocytosis by interacting with DCVs, the plasma membrane, and protein components of the fusion machinery. To further delineate the role of CAPS in endocrine and neural secretion, the tissue distribution of CAPS was determined. Immunoreactive CAPS I localized exclusively to neural and endocrine tissues including adrenal medulla, pancreatic islets, anterior pituitary, thyroid parafollicular C cells, gastrointestinal G cells, renal juxtaglomerular cells, and gray matter throughout the central nervous system. The results are consistent with a widespread functional role of CAPS in the regulated exocytosis of DCVs in the nervous and endocrine systems.