We have studied the cell-free and cellular synthesis of chromogranins A and B, two immunologically distinct protein families of adrenal chromaffin granules. Two cell-free systems (wheat germ and reticulocyte lysate) were used for translating messenger RNA isolated from bovine adrenal medulla. Two primary translation products could be immunoprecipitated in case of chromogranin A. In the presence of microsomes the two chromogranin A precursors (pre-chromogranins A) were converted into a single protein, apparently by the removal of different signal peptides. For chromogranin B only one precursor (pre-chromogranin B) was translated. In isolated chromaffin cells only one chromogranin A protein was synthesized which corresponded to the processed cell-free translation product. During prolonged incubation this protein became slightly larger and more acidic, probably due to glycosylation in the Golgi region. Chromogranin B is post-translationally converted to a significantly more acidic protein. It is concluded that proteolytic breakdown of newly synthesized chromogranin A and B in chromaffin granules is a slow process comparable to that of the enkephalin precursors. It is not yet known what function these chromogranins have and whether breakdown to smaller subunits is necessary for any function to evolve.