Staining of sickle cells with the fluorescent probes chlortetracycline (a Ca2+ probe) and diindocarbocyanine (a general membrane probe) revealed the presence of Ca2+-containing vesicles which are not found in normal erythrocytes. These vesicles increase in number upon deoxygenation, and are apparently formed by endocytosis, as judged by the use of the extracellular fluorescent probe lucifer yellow. The presence of vesicles is not restricted to any particular morphological or density class of cells in the general population.