Inhibition of secretory granule discharge during exocytosis in sea urchin eggs by polymer solutions. 1. We have investigated the effects of the osmotic pressure exerted by polymer solutions on exocytosis in sea urchin eggs. 2. Exocytosis is prevented by including a variety of polymers of different chemical composition and molecular weight in the sea water surrounding the eggs. Inhibition is complete at a polymer osmolality of 250 mosmol/kg. 3. The increase in membrane capacitance which occurs during exocytosis and which corresponds to the fusion of secretory granules with the plasma membrane is not substantially altered by inhibitory concentrations of polymer. 4. In the absence of the ions present in sea water, these polymers inhibit exocytosis at an osmolality of 950 mosmol/kg. 5. Calcium, magnesium and sodium ions reduce the polymer osmolality required to prevent exocytosis. 6. A comparison of the effects of monovalent and divalent ions indicates that the divalent ions bind to and stabilize the secretory granule contents. 7. These results demonstrate that polymers prevent exocytosis by preventing dispersal of the granule contents once fusion of the secretory granule with the plasma-lemma has occurred. The ions present in sea water do not promote dispersal, rather, they hinder it. The contribution of ionic fluxes to granule swelling during exocytosis is discussed.