Sickling is believed to be a consequence of intracellular gelation of deoxyhemoglobin S. One theoretical approach to the therapy of sickle cell anemia is direct interference with gel formation. Gelling, therefore, was studied in the presence and absence of inhibitors. In support of the theory that hydrophobic bonds are involved, it was found that lysolecithin and retinol, amphipaths, which interfere with hydrophobic interactions, inhibited gelation. Moreover, Tris (hydroxymethyl) aminomethane and sugars, agents which have been shown to interfere with hydrogen bond-mediated interactions, also inhibited gelation. Raising the osmolality of the solutions with NaCl interfered somewhat with gelation, but to a lesser degree than with Tris or sugars of equal osmolalities. The data suggest that several types of weak interactions are involved in the gelation phenomenon; hydrophobic, hydrogen and electrostatic.