The evidence that the membrane of the pancreatic zymogen granule is permeable to its contained secretory proteins is outlined. Included is a discussion of the nature and characteristics of the equilibrium-dependent release of protein from isolated granules, the evidence for the permeability of the granule membrane to digestive enzyme protein in situ, and the seeming paradox that isolated granules release protein in medium similar to that thought to exist in the cell. The permeability hypothesis is reconsidered here in light of recent claims of stable nonpermeable granules.