1. Whole blood was incubated in physiological conditions with a variety of modifiers capable of modifying hemoglobin. Some of these compounds have been considered as therapeutic agents for certain hemoglobinopathies such as sickle-cell disease. 2. The extent of modification on hemoglobin was estimated by electrophoresis and the red-cell morphology by scanning electron microscope. 3. Results indicated that carbamyl phosphate, aspirin and glutaryl-salicylamide had no observable effect, whereas cross-linkers in general produced drastic changes in red-cell morphology. 4. Dibromoaspirin, a very effective acetylating agent, produced abnormalities even in concentrations as low as 1 mM.