The clinical and hematologic characteristics of 38 children with subacute and chronic myelomonocytic leukemia (S & CMMOL) are described, and the prognostic significance of these characteristics as recorded at diagnosis is reported. The common and distinctive feature of these children was the excessive proliferation of cells of neutrophilic and monocytic series. The disease predominated in younger children, 95% were younger than 4 years, and boys were more affected than girls (22/16). The onset of the disease was heralded most often by acute or subacute symptoms. Splenomegaly was the most common physical finding at diagnosis. Leukocytosis was usually under 100 X 10(9)/l. Monocytosis and granulocytosis were often associated with normoblastosis, and, in some cases, with moderate blastosis (less than or equal to 30%). Severe anemia and marked thrombocytopenia were found in about one third of patients, increased fetal hemoglobin levels in 53%, and increased gamma-globulin levels in 50% of cases. The Philadelphia chromosome was absent in all blood and marrow cell karyotypes. Thirty-three of 38 patients were treated with moderate or intensive chemotherapy, and in all cases treatment never resulted in a complete remission. Terminal acute leukemia occurred in 11 cases. Of the 38 patients, 29 have died (median survival time, 16 months). Initial characteristics predicting a short survival (log-rank test) included: older age (greater than or equal to 2 years) (P less than 0.001), hepatomegaly (P less than 0.05), bleeding (P less than 0.001), thrombocytopenia (P less than 0.01), high counts of blasts and normoblasts in peripheral blood (P less than 0.01, P less than 0.01). Sex, infections, cutaneous manifestations, lymphadenopathy, degree of splenomegaly, hemoglobin levels, fetal hemoglobin, leukocyte counts, percent of blasts in bone marrow, and serum gamma-globulin levels were of no prognostic value. When survival was plotted on a semilogarithmic scale, a change in death rate was evident at the second year of survival suggesting that there may be two subgroups of patients with myelomonocytic picture, one with very rapid, and another with a slower rate of mortality. A stepwise discriminant-function analysis was performed in an attempt to distinguish between those children who lived less than or equal to 2 years and those who lived longer. A linear combination of variables which best discriminated between these two subgroups was found. Nearly all patients could be classified as a short-survivor or long-survivor on the basis of age and platelet, blast, and normoblast counts in peripheral blood.(ABSTRACT TRUNCATED AT 400 WORDS)