Our previous studies on the mechanism by which citrate agar electrophoresis separates hemoglobins led to the conclusion that hemoglobins bind to at least some sulfated polysaccharides. In the present report, we describe our deduction at the location of the binding site on the hemoglobin molecule. This led to the prediction, on theoretical grounds, that the anionic polysaccharides should possess anti-gelling actions toward hemoglobins and might be useful drug models. We have shown that anionic polysaccharides including heparin, lambda-car-rageenan, dermatan sulfate, fucoidan, and agaropectin have anti-gelling activity.Evidence indicates that heparin can be introduced into red cells by synthetic lipid vesicles (liposomes) and that, once introduced, acts to block sickling. Because of the high solubility and low toxicity of the polysaccharides, we propose that these compounds deserve further study as potential anti-sickling agents.