The ultrastructual and immunologic features of the initial Reed-Sternberg and Hodgkin cells are compared with the ultimate leukemic cell type in a child with Hodgkin's disease who subsequently developed acute myelomonocytic leukemia (AMML) following 29 months of chemotherapy. Hodgkin tumor cells contained cytoplasmic IgG and ultrastructurally resembled large immunoblasts, containing one or two round nuclei with large bizarre nucleoli, many polyribosomes, sparase endoplasmic reticulum, underdeveloped Golgi lamellae, and few cytoplasmic granules. The Hodgkin tumor cells displayed no evidence of phagocytosis. The leukemic monocytic cells did not contain cytoplasmic IgG and, ultrastrucally, exhibited and indented and irregular nuclear profile with less prominent nucleoli, numerous pleomorphic granules, a moderate number of free ribosomes, short segments of endoplasmic reticulum, and stacked Golgi lamellae. The cell surface was irregular and occasionally appeared involved in endocytic activity. These results indicate that the Hodgkin tumor cells originated from B lymphocytes rather than tissue macrophages, whereas the leukemic monocytes arose from the bone marrow-derived monocyte-macrophage series. The findings suggest further that AMML developing after Hodgkin's disease consitutes a second neoplasm rather than a leukemic transformation of Hodgkin tumor cells.