The passage of erythrocytes through the walls of splenic sinuses was studied in rats treated with phenylhydrazine. The sinus wall contained no preformed apertures. Instead, erythrocytes and other cells passing through the spleen entered interendothelial slits and squeezed through. The presence of phenylhydrazine-induced Heinz bodies within erythrocytes impeded their transmural passage. Normally, few erythrocytes were found in transit across the walls of sinuses. However, after phenylhydrazine, many of the interendothelial slits in sinuses were occupied by damaged erythrocytes. Virtually all of the interendothelial slits in sinuses appeared capable of passing erythrocytes. The slits seldom exceeded 0.2-0.5 µ in width, even with an erythrocyte in passage. Bands of intraendothelial microfilaments running alongside the interendothelial slits appeared to have a major role in causing the slits to remain narrow. Thus, the sinus wall, reinforced by microfilamentous bands, significantly controlled the circulation of erythrocytes through the spleen. Normal red cells were pliant enough to squeeze through, but cells containing large rigid inclusions were held in the slits or delayed in their passage. When many of the slits were occupied by cells slow in passage, the outflow track became blocked, and circulation through the spleen was impeded. Therefore, cells pooled in the cords, macrophages increased in number, and the sequences initiated that resulted in splenomegaly.