Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic lymphoblasts in 6 patients with acute lymphoblastic leukemia. Similar studies were performed on lymphoblasts from lymph nodes obtained from 10 surgical patients without nodal diseases. Significant quantitative differences between normal and leukemic mitochondria were not observed except for a difference in mitochondrial area per cell (P less than 0.05). This was not significant lacking, qualitative diffecrences were observed. These abnormalities included rare giant mitochondria, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and nucleus during interphase. Fifty-three percent of the leukemic lymphoblasts contained polyribosomes, as compared to 25% of the normal lymphoblasts. The cells with the polyribosomes contained the giant mitochondria. The leukemic lymphoblasts had an appearance similar to transformed lymphocytes resulting from an immunologic stimulus. This suggests that acute lymphoblastic leukemia may be a disease which is associated with an immunologic response. From the available ultrastructural and biochemical data, it would seem that the leukemic lymphoblast is a product of an abnormal metabolism which affects its ability to differentiate. These ultrastructural findings seem to indicate the need for biochemical investigation of leukemic mitochondria. (Am J Pathol 78:49-58, 1975