Over 25 years ago Francis reported an association between blood transfusion and worsened cancer prognosis. Subsequently there has been much debate over whether there is in fact such an association, and if so, what is its underlying mechanism. Allogeneic blood transfusion is the most frequent allo-transplantation procedure performed on a routine basis with no prior HLA-typing. 50% of the recipients of unprocessed red cells and platelets become allo-immunised. It is our proposition that as result of normal physiological ageing and metabolic processes (with depletion of ATP and reduction of active membrane processes), there is leaching of biologically active substances from the cells into stored blood products. These leached bioactive substances have immuno-modulatory effects, which may in part explain the increased likelihood of postoperative sepsis and adult respiratory distress syndrome in transfusion recipients. They also promote cell growth and angiogenesis and may therefore have a direct effect on tumour growth. We provide evidence to support a possible hypothesis which could explain much of the conflicting clinical and experimental evidence.