The development and fate of the secretory granules in murine, rat and human juxtaglomerular epithelioid cells were examined using ultrastructural and immunocytochemical methods. The formation of mature renin granules occurs by fusion of rhomboid protogranules followed by coalescence of their paracrystalline contents, and by the fusion of roundish juvenile granules having an amorphous internum. Protogranules with paracrystalline contents are prominent in animals with stimulated renin synthesis, indicating an overcharge in processing and/or packaging of the secretory product, renin, under these conditions. Various similarities between lysosomes/multivesicular bodies (MVBs) and juvenile renin granules have been observed. With the exception of small MVBs, no renin-negative organelles that could be regarded as lysosomes were found in epithelioid cells of mice and rats. Therefore, we suggest that renin granules are modified lysosomes. Immunocytochemical findings indicate that juvenile secretory granules of epithelioid cells represent the converting and activating compartment for prorenin. Endocytosed foreign tracers such as HRP or cationized ferritin are preferentially internalized by juvenile renin granules, which hence appear to be outstanding by their fusogeneity. Consequently, juvenile granules are probably responsible for the secretion of prorenin, and mature granules for that of active renin.