The influence of erythrocyte shape changes on the sedimentation rate was studied in vitro and in vivo. In vitro the highest sedimentation rate was observed with a slight degree of stomatocytosis (morphological index-0.3; i.e. one red cell out of three being a stomatocyte I). With increasing degrees of stomatocytosis the sedimentation rate gradually decreased. Echinocytosis reduced the aggregation and sedimentation very drastically; the sedimentation rate was virtually zero when echinocytosis I or higher degrees were present. The influence of abnormal cell shapes occurring in vivo was studied in patients with an abnormal blood smear. It was found that a severely abnormal red cell morphology reduced the sedimentation rate in a standardized, fibrinogen-rich plasma to about half. These results indicate that the shape plays a crucial role in the aggregation and sedimentation of red cells and they may contribute to the understanding of the interaction of red cells with other cells such as endothelium.