We investigated the light and ultrastructural morphology of 37 patients with acute nonlymphocytic leukemia (ANLL) and inv(16)(p13q22) or del (16)(q22) with specific emphasis on the changes in the eosinophils (EOS). All but one of the 37 patients were classified as French-American-British M4 with eosinophilia (FAB M4-E) on the basis of the monocytoid nature of the leukemic cells and the presence of large EOS with interspersed basophilic-staining granules. A median of 92% of the blasts were peroxidase positive, and Auer rods were found in 71% of cases. Only 27% of the cases had sufficient alpha-naphthyl butyrate positivity to confirm the diagnosis of FAB M4, but electron microscopy demonstrated a sufficient monocytic component to support this classification in all cases examined. Electron microscopy also demonstrated nuclear blebs both in the blasts and notably, in the EOS of all cases examined (16 of 16). Nuclear blebs in EOS were found in only 1 of 13 cases of ANLL that showed eosinophilia but lacked abnormalities of chromosome 16. This case was also classified as FAB M4-E. The finding of nuclear blebs in EOS in FAB M4-E suggests that the EOS may be derived from the malignant clone in this leukemia. These blebs are also of diagnostic in value classifying a leukemia as FAB M4-E.