Abstract Hemagglutination (HA) of human “O” erythrocytes by reoviruses was found to be similar to that of enteroviruses in its nonenzymatic character and in its inhibition by treatment of the virus with p -hydroxymercuribenzoate (PMB). This inhibiting effect of PMB was reversed by reduced glutathione (GSH). Infectivity and HA declined after incubation of the viruses with PMB and were restored by GSH. Treatment of reoviruses with alkaline N -ethylmaleimide (NEM) did not alter subsequent HA, differing in this respect from results with enteroviruses. Infective reovirus types 1 and 3, but not type 2, were incompletely eluted from erythrocytes after incubation for 48 hours at 20°C. Trypsin treatment of reovirus type 1, but not of reoviruses types 2 or 3 or Coxsackie B5, markedly increased titers of HA and infectivity. The red cell receptor for reovirus HA was removed by incubation with trypsin or periodate but was unaltered by PMB, receptor-destroying enzyme (RDE), or NEM. It is concluded that reovirus-erythrocyte union involves mucoproteins on the surface of each reactant; those on the virus contain SH groups but those of the red cell do not, and, therefore, the essential bond between them may not be SH in nature.