Recent in vitro data have shown that growth factors are more effective when used in combination. This synergy between cytokines, when translated in a clinical setting, should permit a reduction of dosage, and therefore of toxicity. We sought to determine whether the sequential administration of low doses of G-CSF followed by low doses of GM-CSF could be effective both in protecting from neutropenia, and in reducing side effects. A randomized single blind phase III study was carried out. Patients considered to be eligible for the study were designated to receive a minimum of 3 chemotherapy cycles for treatment of metastatic or locally advanced cancer. Patients were randomized to receive, from the 8th day to the 13th day of cycle, G-CSF, 2.5 micrograms/kg/day s.c., or G-CSF, 2.5 micrograms/kg/day s.c. for the first 3 days, followed by GM-CSF, 2.5 micrograms/kg/day s.c. for the last 3 days. The number of delays in relation to the number of cycles, the number of patients whose therapies were deferred, and the total number of days of delay in relation to the total number of days of observation were significantly different, with far fewer delays in the group treated with the G-GM sequence. Our study confirms that the sequential administration of G-CSF and GM-CSF is highly synergistic. This synergy allows clinicians to administer chemotherapy treatments to pre-treated and/or elderly patients, with minimal risk of toxicity and no need for delays or dosage reduction.