Two compounds that inhibit the sickling of erythrocytesin vitroare sodium cyanate and glyceraldehyde. The former compound reacts selectivity with the NH2−terminus of the a-chain of hemoglobin S and thereby leads to an increased oxygen affinity of the protein and inhibition of erythrocyte sickling. The toxicity associated with oral administration of sodium cyanate precludes its use in the treatment of sickle cell anemia; administration by extracorporeal routes is still under consideration. The compound glyceraldehyde also inhibits the sickling of erythrocytesin vitrobut does so by a different mechanism than sodium cyanate; it interferes directly with the gelation of deoxyhemoglobin S. Glyceraldehyde also displays selectivity; only five of a total 24 amino groups per αβ dimer of hemoglobin S are reactive. Preclinical studies on this compound as a potential treatment for sickle cell anemia are in progress.