A previous phase II study (CALGB 9132) of etoposide/cisplatin + rG-CSF in patients with advanced non-small cell lung cancer (NSCLC) showed a marked difference in the absolute neutrophil count (ANC) nadirs between courses 1 and 2. Median ANC nadirs for courses 1 and 2 were 200 and 2500, respectively, suggesting a priming effect for rG-CSF. The present study was designed to determine whether rG-CSF given prior to the first cycle of chemotherapy would decrease the severity and duration of neutropenia. Twelve patients with stage IIIB or IV NSCLC and performance status 0-1 received rG-CSF 5 microg/kg for 5 consecutive days starting 7 days before treatment with etoposide 200 mg/m2 on days 1-3 and cisplatin 35 mg/m2 on days 1-3, repeated every 3 weeks. Patients also received rG-CSF 5 microg/kg s.c. day 4 to postnadir ANC > 10,000. The median WBC nadir, ANC nadir, and platelet nadir after the first cycle of chemotherapy in the historical group (CALGB 9132) were 1300 cells/microl, 200 cells/microl, and 80,000 cells/microl, respectively. In the present study, the median WBC nadir, ANC nadir, and platelet nadir were 1300 cells/microl, 144 cells/microl, and 56,000 cells/microl, respectively. The median time for ANC to reach 10,000 cells/microl was 15 days in both the historical and the present study. For course 2, the WBC, ANC, platelet nadirs, and duration of grade 4 neutropenia were 2600, 1450, 70,000, and 0 days, respectively. This study failed to show a priming effect for rG-CSF when given in this dose and schedule.