Twenty-five cases of acute myelomonocytic leukemia (AMMoL) and acute monocytic leukemia (AMoL) treated at the Kitasato University Hospital from 1975 to 1984 are reviewed in respect of the incidence, clinical course, treatment and prognosis of the central nervous system (CNS) and skin involvement. Morphological diagnosis of acute leukemia was made according to the FAB classification. CNS involvement was present in 6 (24%), and skin involvement proven by biopsy in 9 (36%). Those patients with younger age, superficial lymphadenopathy, hepatomegaly, splenomegaly, high peripheral white blood cell count, and elevated serum LDH and lysozyme activities on admission showed a high incidence of CNS and skin involvement during thier clinical course. Radiotherapy and surgical resection were temporarily effective for the treatment of leukemic skin infiltration. However, leukemic skin lesions were generally so multiple and extensive that all patients with skin involvement required systemic chemotherapy. In 5 patients, CNS infiltration ocurred at the time of hematological recurrence, and was refractory to the treatment. All patients with CNS involvement were treated with intrathecal methotrexate, cytosine arabinoside and hydrocortisone, and only one of them achieved CNS remission. Therefore, prophylactic treatment for CNS involvement is necessary in patients who have risk factors as listed above. The high incidence of CNS and skin involvement in patients with AMMoL and AMoL is thought to be related to the prolongation of survival due to the recent improvement of treatment as well as the characteristics of leukemic cells.