Submicroscopic aspects of the adherence of Group A streptococci to HEp-2 cells and the time sequence of their further interaction with these cells were studied. The M+ variant of streptococci, characterized by the presence of filamentous protrusions on the cell wall, displayed a high capacity for adherence, in contrast to the M- variant of the same strain, where adherence was low. The first stage of the interaction between M+ variant of Group A streptococci and HEp-2 cells was adherence of the filamentous protrusions of the bacterial cell wall to host cell cytoplasmic membrane; this was followed by closer contact of the streptococcus cell wall with HEp-2 cell surface. Continuing incubation led to the development of invaginations in the cytoplasmic membranes of HEp-2 cells, into which streptococci gradually penetrated. Ingestion of streptococci into the forming pseudovacuoles of the host cell was accompanied by bacterial cell division, culminating in total disintegration of the host cell and release of the streptococci into the medium. At all stages of the interaction there was a pronounced tendency to form multiple contacts between the surface structures of the streptococcus cell and the membrane structures of the animal cell being attacked.