High-dose chemotherapy with autologous hematopoietic stem cell transplantation has been expected to result in a promising outcome in high risk aggressive non-Hodgkin's lymphoma (NHL). However, it remains unknown what type of initial chemotherapy is optimal, especially regarding progenitor cell mobilization. Sixty-three untreated patients with aggressive NHL in a high risk group were randomized to either a biweekly arm with 8 cycles of standard CHOP or 6 cycles of the dose-escalated CHOP arm with cyclophosphamide 1.5 g/m2 and doxorubicin 70 mg/m2. Lenograstim (glycosylated rHuG-CSF 2.0 microg/kg/day) was administered daily from day 3 to patients in both arms. The mobilization effect of the two regimens on circulating CD34+ cells was evaluated. Twenty-seven of 29 patients in the biweekly CHOP arm and 33 of 34 patients in the dose-escalated CHOP were assessable. Dose-escalated CHOP yielded a significantly higher number of circulating CD34+ cells in the first cycle compared with biweekly CHOP (p=0.05). The peak number of circulating CD34+ cells with biweekly CHOP did not significantly change from cycle to cycle; however, in dose-escalated CHOP, the peak number of circulating CD34+ cells mobilized after the fifth and sixth cycle was lower than after the first cycle (p=0.07 and 0.009, respectively). Routine conventional-dose chemotherapy and low-dose G-CSF can mobilize sufficient CD34+ cells in patients with aggressive NHL. The mobilization kinetics of circulating progenitor cells in patients with aggressive NHL is dependent on the dosage and schedule of CHOP.