Treatment of human group O and sheep erythrocytes with receptor-destroying enzyme rendered them inagglutinable by simian rotavirus SA-11. The erythrocyte receptors were also removed by periodate oxidation and markedly reduced by incubation with a high concentration of trypsin, but they were not altered by infectivity-enhancing concentrations of trypsin, p-hydroxymercuribenzoate, or sodium sulfite (Na2SO3). Hemagglutinating activity of the virus particles was destroyed by periodate oxidation at 37 degrees C, p-hydroxymercuribenzoate, and a high concentration of trypsin and decreased by Na2SOa but was not altered by incubation with receptor-destroying enzyme, infectivity-enhancing concentrations of trypsin, or periodate oxidation at 4 degrees C. These results indicate that neuraminic acid-containing receptor substances are involved in the interaction of the virus with human and sheep erythrocytes, and suggest that SA-11-erythrocyte union involves carbohydrate on the surface of erythrocytes but not on the virion. Sensitivities of the SA-11 hemagglutinin to alcohols and repeated freeze-thaw cycles were also investigated.