AbstractThe plasma of a patient being prepared for allogeneic bone marrow transplantation was found to be severely lymphocytotoxic to donor cells. Three isovolaemic plasma exchanges carried out using a continuous‐flow technique were required to reduce this titre to undetectable levels. Neither these procedures nor pretransplantation conditioning of the patient with 60 mg/kg or cyclophosphamide on two consecutive days resulted in overt haemolysis. However, a single identical plasmapheresis 12 hours after completing the second dose of the alkylating agent resulted in profound intravascular haemolysis requiring red cell transfusion. Subsequent studies in five patients receiving the same cyclophosphamide regimen demonstrated that red cell life span, when measured with radio‐chromium, was reduced from a normal of 25–35 days to a median of 11.5 days. Further studies in the same five patients carried out simultaneously demonstrated that red cell fragility, when assessedin vitrowith osmotic or mechanical stress, was marginally increased but became clearly abnormal in only one individual. These doses of cyclophosphamide may result in accelerated but subclinical red cell destruction, and plasma exchange in this period may be associated with rapid intravascular haemolysis. This complication should now be added to the list of those that can occur when plasmapheresis is required in this specific clinical situ