At present, central nervous system (CNS) leukemia is one of the principal causes for termination of complete remission in acute lymphocytic leukemia (ALL). The factors which influence the increase of CNS infiltration have been studied comparing different parameters (age, initial peripheral WBC count, type of leukemia, and presence or absence of initial organomegaly) to determine the leukemia population with highest risk of developing this syndrome. A total of 127 cases of acute lymphoid leukemia (ALL) (98 children and 29 adults) and 101 acute myelocytic leukemia (AML) (41 children and 60 adults), on the same treatment protocol from 1967 to 1970, were included in this study. The median survival and the rate of incidence of symptomatic CNS leukemia was 18 mo and 32% in ALL and 4 mo and 7% in AML. The incidence of CNS leukemia per month of survival was similar in both groups: 4 mo, 3% in AML and 4% in ALL, at 8 mo, 13% in both ALL and AML. The incidence of CNS leukemia was higher in children with ALL than in adults: 41% in children and 19% in adults at 20-mo survival. Organomegaly (spleen, liver and/or lymph nodes) as an early manifestation increased the risk of CNS involvement. The CNS infiltration was significantly greater in patients with high initial peripheral WBC count. The incidence of meningeal leukemia did not differ in ALL and AML. In conclusion, CNS leukemia infiltration was more frequent in children with initial organomegaly and high WBC count at the time of diagnosis.