In order to evaluate a method permitting quantitation of splenic red blood cell destruction, a model of erythrocyte destruction in enlarged spleens was created: Erythrocytes are destroyed in the splenic erythrocyte pool at a constant rate, producing in labelling studies hyperhaemolysis due to random destruction. A mathematical analysis of the model shows that the splenic destruction rate can be calculated with great accuracy from quantitation of the initial excess radioactivity, measured over the spleen during the first days after infusion of 51-Cr-labelled autologous erythrocytes. 18 patients with splenomegaly (479-4700 g) were investigated. The splenic erythrocyte destruction rate was estimated to be between 0.5-4.4% of the total erythrocyte mass per day, increasing significantly with increasing splenic weight. The results indicate that erythrocyte destruction takes place almost exclusively in the enlarged spleen in cases of predominant splenomegaly without complicating immunohaemolysis.