While blood transfusion is increasingly implicated in the aetiology of tumour recurrence, the mechanism of this effect is unclear. Cancer-bearing patients are known to have factors in their sera which depress the function of normal lymphocytes. It is possible that blood transfusion accentuates this natural suppression. An animal model was therefore developed to study the effect of blood transfusion on humoral immunosuppressive activity and its possible relationship to red cell clearance. WAG rats given a transfusion of chromium-labelled allogeneic but blood-group compatible DA rat blood, developed significantly increased (P < 0.001) levels of lymphocyte suppressive factors in plasma (maximum at 7 days) which coincided with accelerated red cell clearance (t1/2 = 7 days). A transfusion of syngeneic WAG blood caused only a small transient increase in plasma suppression and red cells were cleared at a normal rate (t1/2 = 13 days) consistent with previous studies. However, when syngeneic WAG red cells were lysed and the red cell membranes infused there was a rapid increase in plasma suppression (P < 0.001), similar to but less prolonged than that achieved with allogeneic blood. The immunosuppressive effect of blood transfusion may result from accelerated clearance of allogeneic or damaged syngeneic red blood cells.