Hemadsorption (HAD) induced in HEp-2 cells infected with vaccinia virus was observed. In ultrathin sections, binding of 36 red blood cells (RBCs) was examined in detail and 3 types of HAD were observed: (1) direct and close binding of RBCs to infected HEp-2 cells (cyto-HAD) was observed in cross sections of 27 RBCs (2) binding of RBCs through microvilli of infected cells was found in 11 RBCs, and (3) five RBCs were distorted to form tentacle-like projections by which they were bound to the HEp-2 cell surface. Scanning electron microscopy revealed that more than 30% of the RBCs were bound to microvilli of vaccinia virus-infected HEp-2 cells, and that the number of microvilli twined round each RBC was over ten, RBCs were attached to certain microvilli through swollen sucker-like tips which were not observable in non-infected HEp-2 cells. RBCs sometimes revealed a polygonal shape at regions of binding to microvilli. Virion-mediated RBC HEp-2 cell binding could not be observed.