The ability of lymphocytes, monocytes and polymorphonuclear leucocytes (PMN) to mediate antibody-dependent cellular cytotoxicity (ADCC) against varicella-zoster virus (VZV) infected fibroblasts was tested in 51Cr release and single-cell assays. Lymphocytes had the greatest lytic activity, monocytes were intermediate in activity and PMN were the least active. Lymphocyte-mediated ADCC was complete by as early as 4 h, while maximal monocyte and PMN-mediated ADCC required 18 h. In single-cell assays, monocytes formed conjugates with both uninfected and VZV-infected targets, but did not cause lysis. PMN failed to bind or lyse either target. Few lymphocytes formed conjugates with uninfected targets, while a higher percentage bound to VZV-infected targets and caused lysis. In the presence of human antibodies to VZV conjugate formation and lysis of VZV-infected targets was significantly increased with each of the effector-cell populations. Lymphocytes had the highest lytic activity in single-cell assays as well as in 51Cr release assays, and were responsible for most of the ADCC detected in adult peripheral blood against VZV-infected targets.