The in vitro lysis of varicella-zoster virus (VZV) infected human fibroblasts by blood mononuclear cells (MNC) is inhibited by cyclosporin A, whether or not the effector and target cells chare HLA A or B antigens. Interleukin 2 (IL-2) reversed the inhibition by cyclosporin A (CyA) and also induced a further increase in target cell lysis by MNC in the absence of CyA. MNC depleted of OKM-1+ or Leu-11+ cells showed reduced lysis of VZV infected fibroblasts and this reduction was not overcome by adding IL-2. Depletion of monocytes from the MNC effectors reduced target cell lysis and this effect was reversed by adding Interleukin 1 (IL-1). The results indicate that NK cells contribute to the lysis of VZV infected cells and suggest that IL-2 release by T cells, as a result of HLA matching or antigen representation, may amplify this mechanism.