A number of intracellular, membrane-bound compartments in both the endocytic and exocytic pathways of eukaryotic cells have an acidic internal pH. In endocrine cells, the mature secretory vesicle has an acidic pH; secretory vesicles isolated from exocrine cells, however, appear to have a neutral pH. Recently we have used a newly developed immunocytochemical technique to map low-pH compartments in insulin-secreting islet cells with the electron microscope and find that during the maturation of the secretory vesicle there is a progressive acidification of these vesicles that begins as soon as the trans Golgi condensing vacuoles form. Now we have used this technique to examine two exocrine cells: the pancreatic acinar cell and the parotid serous cell. In both cell types, the trans Golgi condensing vacuoles are acidic and accumulate the low-pH probe to the same extent as condensing vacuoles of insulin-secreting islet cells. Unlike insulin-secreting cells, however, maturation of the granules is accompanied by a return of luminal pH to near neutrality. Therefore, although the pH of storage granules in exocrine and endocrine cells is different, the pH of the condensing vacuoles in both cells is acidic.