The activity of recombinant human growth hormone (rhGH) in enhancing CD34+ cell mobilization elicited by chemotherapy plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated in 16 hard-to-mobilize patients, that is, those achieving a peak of circulating CD34+ cells 10/μL or less, or a collection of CD34+ cells equal to or less than 2 × 106/kg. Patients who had failed a first mobilization attempt with chemotherapy plus rhG-CSF (5 μg/kg/d) were remobilized with chemotherapy plus rhG-CSF and rhGH (100 μg/kg/d). As compared with rhG-CSF, the combined rhGH/rhG-CSF treatment induced significantly higher (P ≤ .05) median peak values for CD34+ cells/μL (7 versus 29), colony-forming cells (CFCs)/mL (2154 versus 28 510), and long-term culture-initiating cells (LTC-ICs)/mL (25 versus 511). Following rhG-CSF and rhGH/rhG-CSF, the median yields of CD34+ cells per leukapheresis were 1.1 × 106/kg and 2.3 × 106/kg (P ≤ .008), respectively; the median total collections of CD34+ cells were 1.1 × 106/kg and 6 × 106/kg (P ≤ .008), respectively. No specific side effect could be ascribed to rhGH, except a transient hyperglycemia occurring in 2 patients. Reinfusion of rhGH/rhG-CSF-mobilized cells following myeloablative therapy resulted in prompt hematopoietic recovery. In conclusion, our data demonstrate that in poor mobilizers addition of rhGH to rhG-CSF allows the patients to efficiently mobilize and collect CD34+ cells with maintained functional properties. (Blood. 2004;103: 3287-3295)