Hemolysis by Sendai virus has been assayed in a system of erythrocytes attached in monolayer fashion to plastic surfaces by poly- l-lysine. Immobilization of cells in this way allowed the easy performance of multiple-step experiments in which the effect of virus was studied in conjunction with lectins and antibodies. The binding of these ligands immediately prior to or after the adsorption of virus particles to erythrocyte monolayers had a marked inhibitory effect on viral hemolysis. Different patterns of hemolysis resulted according to the specificity of the lectins and antibodies with respect to the virus receptor. Con A, Ricinus communis agglutinin, and anti-Sendai antibodies, reacting with receptors distinct from the sialoglycoprotein, did not interfere with the adsorption process of the virus to the membrane. They inhibited hemolysis exclusively by a restriction of the mobility of elements in the cell membrane and in the viral envelope. Phytohemagglutinin, wheat germ agglutinin, and anti-glycophorin antibodies, on the other hand, inhibited lysis by interference with elements including the virus receptor. It is concluded that the induction of hemolysis requires the specific binding of the virus to a receptor and that rearrangement of elements in both the viral envelope and the plasma membrane have to follow this adsorption. These subtle molecular rearrangements are a prelude to virus-cell fusion in which disintegration of the viral envelope structure is observed. This latter process could be characterized by monitoring the expression of virus and/or host-specific antigens with immune fluorescence techniques. Reactions of virus-bound erythrocytes with anti-host did not interfere to a detectable degree with the subsequent binding of anti-viral antibodies. In contrast, antibodies directed against virus-specific antigens and attached to virus-bound erythrocytes at 4° but not at 37° inhibited the subsequent reaction of virus with anti-host. We conclude that two types of host antigens exist: those accessible in intact virus particles and closely associated with the distal portion of those viral proteins forming spikes, and those antigens reactive only after the dispersal of the elements of the viral envelope folowing its fusion with the cell surface.