The collection efficiency (CE) of the Fenwall CS3000 continuous flow blood cell separator in the apheresis of peripheral blood stem cells during haemopoietic recovery following myelosuppressive chemotherapy was analysed. Ninety-three apheresis were performed in 19 patients using procedure 3 on the Fenwal CS3000. The overall CE was calculated from the pre-apheresis cell counts and the stated blood volume processed. Instantaneous CE was calculated from cell counts in the inlet and return lines. The overall mononuclear cell and granulocyte-macrophage colony forming unit CE were 64.0% and 55.8%, respectively, significantly lower than the instantaneous CEs of 94.5% and 95.4%, respectively (P = 0.0001, t test, for both comparisons). Three factors unrelated to machine performance contributed to the lower overall CE despite a high instantaneous CE: (1) A fall in the patient's mononuclear cell counts during apheresis leading to an overestimation of the cells available for collection, (2) dilution of blood by anti-coagulant, and (3) the operational dead space of the Fenwal CS3000. The overall CE corrected for these 3 factors approximated the instantaneous CE closely. Thus there is little room for further enhancement of machine performance because the Fenwal CS3000 is already operating with a very high instantaneous CE. To achieve major improvement in the yield of peripheral blood stem cell harvests, more effective mobilization protocols and better timing of apheresis are required.