Electron micrographs of blastic human lymphocytes from phytohemagglutinin (PHA) cultures showed normal mitochondria with round, oval, and elongated shapes, containing well-defined cristae and electron-dense matrix. Micrographs of blastic lymphocytes from PHA cultures with ethidium bromide (EB) at 1 to 3 μg/ml, however, showed swollen mitochondria with fewer cristae and vacuolated matrix. Similarly damaged mitochondria were observed in micrographs of blast cells from patients with acute lymphoblastic (ALL) and acute myeloblastic leukemia (AML) and also in lymphocytes from cases of prolymphocytic leukemia (PLL). This study shows specific structural damage to mitochondrial cristae in normal proliferating lymphocytes when their mitochondrial DNA transcription, hence protein synthesis, is selectively inhibited by EB. It confirms that damaged cristae give structural evidence of inhibited mitochondrial protein synthesis. The structural damage of mitochondrial cristae observed in a variety of leukemic cells suggests that mitochondrial protein synthesis may be disturbed or abnormal in leukemic cells.