In a retrospective study, we showed that a monocyte count of <150/&mgr;l on days 6 to 8 might be a predictor of grade III or IV neutropenia during cancer chemotherapy given at 3- or 4-week intervals. In the present study, we investigated whether the administration of granulocyte colony-stimulating factor (G-CSF) when monocytopenia appears lessens neutropenia during chemotherapy for lung cancer. Between June 1997 and August 1998, 60 patients who received chemotherapy at 3- or 4-week intervals for unresectable lung cancer were randomized to receive G-CSF (2 &mgr;g/kg or 50 &mgr;g/m2) when monocytopenia (<150/&mgr;l) appeared on days 6 to 8 after chemotherapy (group A) or when neutropenia (<1,000/&mgr;l) or leukopenia (<2,000/&mgr;l) appeared after chemotherapy (group B). The administration of G-CSF was stopped when the leukocyte or neutrophil counts reached >10,000/&mgr;l or 5,000/&mgr;l, respectively. The blood cells counts were examined three times a week and the degree, duration, and frequency of chemotherapy-induced neutropenia of the two groups were compared. One patient in group A was excluded because whole brain irradiation during chemotherapy was required. Twenty-nine and 30 patients in groups A and B, respectively, received platinum-based chemotherapy and their chemotherapy-induced hematologic toxicities were analyzed. The mean neutrophil count nadir of group A (1,558 ± 1,771/&mgr;l) was significantly higher than that of group B (810 ± 639/&mgr;l,p= 0.032). The duration of grade III neutropenia in group A (1.4 ± 1.7 days) was significantly shorter than that in group B (2.9 ± 1.9 days,p= 0.004), and the frequency of grade III neutropenia in group A (48%) was significantly lower than that in group B (83%,p= 0.002). Infectious episodes occurred in five and eight patients in groups A and B, respectively. The durations of G-CSF therapy required by group A and B patients (4.8 ± 3.1 vs. 4.7 ± 2.7 days) were not significantly different. Prophylactic administration of G-CSF did not exacerbate anemia or thrombocytopenia induced by chemotherapy. We conclude that the prophylactic administration of G-CSF when monocytopenia appears can lessen neutropenia caused by chemotherapy for lung cancer without increasing the total G-CSF dose.