A randomised crossover trial of two separators was undertaken to compare the mononuclear cell, CD34+ cell and CFU-GM yield, in patients (<61 years) with previously untreated symptomatic multiple myeloma. After first-line therapy, all patients received mobilising chemotherapy (cyclophosphamide 4 g/m 2 ) and daily G-CSF. The first leucapheresis was performed on the first day the peripheral blood absolute CD34+ cell count was > 20 cells/ll. All patients underwent 2 leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra. The target duration of the procedure on the COBE Spectra was 2 total blood volumes, and for the Haemonetics MCS+ it was 20 cycles with four recirculations. Between September 2003 and March 2005, 60 patients were entered in the study. COBE Spectra version 6 processed significantly larger volumes of blood than the Haemonetics MCS+ (8,845 and 5,680 ml, respectively, P < 0.01). The absolute yield of mononuclear cells (2.1 vs. 1.5 β’ 10 8 /kg, P ΒΌ 0.04), CFU-GM (11 vs. 3 β’ 10 4 /kg, P ΒΌ 0.01) and CD34+ cells (3 vs. 1.7 β’ 10 6 /kg, P ΒΌ 0.02) were all significantly higher with the COBE Spectra version 6, as were the yields per unit volume of blood processed. In conclusion, our study shows that COBE Spectra Version 6 is faster and has a better yield than the Haemonetics MCS+, in patients with multiple myeloma.