Cyanate is undergoing study as a drug to prevent occlusive sickle cell crises. Carbamylation of hemoglobin S increases its oxygen affinity, thereby decreasing its tendency to aggregate at low oxygen tensions. The cell membrane has also been shown to be carbamylated. We studied the effect of carbamylation on deformability of sickle, normal, and stored normal erythrocytes. Deformability was measured as filtration time of erythrocyte suspensions through 3-µ polycarbonate filters. Oxygenated carbamylated sickle erythrocytes had a marked shortening of filtration time that could not be explained by changes in morphology. In addition, normal erythrocytes became more filterable with carbamylation. Decreased filterability after storage at 4°C for 48 hr was returned to normal following carbamylation and incubation with glucose. No correlation was made with changes in either morphology, cell size, or ATP levels. Therefore, it was postulated that carbamylation affected filterability by binding either the cell membrane or cell contents or both.