The effect of recombinant human erythropoietin (rHuEPO) on the anemia of cancer was examined in 15 children with hematologic malignancies (group I) and solid tumors (group II), whose hemoglobin (Hb) was under the third percentile for sex and age. The response to rHuEPO was defined as an increase of Hb to above the 10th percentile following 8 weeks of therapy. The rHuEPO caused an increase in the Hb and hematocrit (Hct) in 46% of children of both groups at a dose of 150 IU/L, in 28.5% of children at a dose of 250 IU/L and in 25.5% of children at a dose of 400 IU/L. Leukocyte and platelet counts were not influenced by the rHuEPO treatment. The red cell transfusion requirement decreased to 66% in both groups after rHuEPO treatment. Erythropoietin (EPO) levels were measured prior to the treatment and then every 4 weeks during rHuEPO treatment. Children who responded to EPO had an initial EPO level of < 100 IU/L, while those who did not respond had an initial EPO level of > 100 IU/L. Erythropoietin was well tolerated in all children, with no side effects.