Recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and granulocyte colony-stimulating factor (rhG-CSF) enhance neutrophil recovery following autologous bone marrow transplantation (ABMT) for malignant lymphoma. Based on findings in preclinical studies, a phase I-II trial was conducted to assess the safety and efficacy of the sequential administration of rhIL-3 and rhGM-CSF after bone marrow ablative cytotoxic therapy and ABMT for patients with malignant lymphoma. Thirty-seven patients (20 with non-Hodgkin's lymphoma and 17 with Hodgkin's disease) were treated with intensive cytotoxic therapy before ABMT. Patients were treated in one of four cohorts to receive rhIL-3 (2.5 or 5.0 microg/kg/d) administered by subcutaneous injection for either 5 or 10 days following ABMT. Twenty-four hours after the last dose of rhIL-3, rhGM-CSF (250 microg/m2/d as a 2-hour intravenous infusion) administration was initiated. Sequential cytokine therapy post-ABMT resulted in fewer days of platelet and red blood cell transfusions than seen in historic controls with rhIL-3, rhGM-CSF, or rhG-CSF monotherapy. These data suggest that the sequential administration of rhIL-3 and rhGM-CSF after ABMT results in rapid recovery of multilineage hematopoiesis.