It is logical to expect that large-volume leukapheresis may be able to collect adequate numbers of PBSC with fewer procedures. To date, there is no agreement on the optimal volume of leukapheresis. Therefore, in this study we compared 81 volume with 121 and assessed whether a 50% increase in the blood volume processed would decrease the number of leukaphereses each patient needed to collect greater than or equal to2.5 x 10(6) CD34(+) cells/kg in normal mobilizers. PBSC mobilization was done with cyclophosphamide etoposide followed by rhG-CSF in all patients. Forty patients were randomized to undergo 81 leukaphereses (n = 20 patients) or 121 leukaphereses (n = 20). The median numbers of leukaphereses required in order to collect greater than or equal to2.5 x 10(6) CD34(+) cells/kg in patients processed with 81 and 121 were 1 (range 1-5) and 1 (1-4), respectively (P = 0.50). The median number of total nucleated cells (TNC) collected per patient was greater for the 121 group (7.47 x 10(8)/kg vs 3.90 x 10(8)/kg, P < 0.001), as was the median number of total mononuclear cells (TMNC) (4.26 x 10(8)kg vs 2.16 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+) cells collected per patient (8.94 x 10(6)/kg vs 8.60 x 10(6)/kg, P = 0.85). The TNCs and TMNCs collected per leukapheresis were again greater for the 121 group (3.64 x 10(8)/kg vs 1.91 x 10(8)/kg, P = 0.001 and 2.17 x 10(8)/kg vs 0.88 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+) cells collected per leukapheresis (3.98 x 10(6)/kg vs 3.26 x 10(6)/kg, P = 0.90). This study showed that there is no difference between 81 and 121 volumes in regard to collected CD34(+) cells/kg and also the use of a 121 leukapheresis volume did not decrease the number of leukaphereses performed compared with a 81 leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage of adding 60 min to the time the patient was on the machine.