In this study we have determined which Ga proteins are associated with the pancreatic zymogen granule membrane. The purity of the granule preparation was evaluated both morphologically and biochemically, These studies demonstrated that the isolated zymogen granules were free of any significant cross contamination from other organelles including the plasma membrane, Western blot analysis showed that Go alpha, Gq alpha, and Gs alpha are associated with the zymogen granule membrane, but that Gi1 alpha, Gi2 alpha, and Gi3 alpha are not, The location of these G alpha proteins suggests that they may modulate regulated exocytosis in the pancreatic acinar cell. (C) 1997 Academic Press.