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The mechanisms by which the hemoglobin genotype AS protect against severe malaria are not fully understood. We have investigated the possibility that protection might be achieved through an inability of red blood cells (RBC) with the AS genotype to form rosettes with RBC infected by Plasmodium falciparum. No evidence was obtained to support this hypothesis because RBC with the AS genotype formed rosettes with wild isolates of P. falciparum as readily as RBC with the AA genotype. However, the previous finding that parasitized RBC form rosettes more readily with RBC belonging to group A or B than with RBC belonging to group O was confirmed even in fresh clinical isolates.