In this investigation, the cells of eight patients with acute promyelocytic leukemia were followed by light and electron microscopy. Promyelocytes from untreated patients were filled with large, splinter-shaped granules. The granules were lysosomes, with some showing the ultrastructural features of Auer bodies. In cases responsive to chemotherapy, promyelocytes contained only infrequently splinter-shaped lysosomes, while most lysosomes were of more uniform size and shape. The persistence of large numbers of splinter-shaped lysosomes within promyelocytes was associated with episodes of disseminated intravascular coagulation less responsive to heparin treatment. Promyelocytes from patients in remission were similar to promyeloctyes from nonleukemic bone marrow. The ultrastructural differences in lysosome morphology provide a better criterion for distinguishing malignant from normal promyelocytes than previously detectable by light microscopy alone.