Continuous rabbit cornea cells and cells grown from the stromal layer of corneas excised from New Zealand white rabbits were infected with herpes simplex virus (HSV) strain RE and examined for cytolysis (51Cr release) by antibody-dependent cellular cytotoxicity (ADCC). These sources of lymphocytes from normal animals were used as effector cells: blood, spleen, and lymph nodes. Specific activity was observed in over 75% of rabbits with all three effector cell types, using immune serum from a rabbit a 21 days after infection. Activity was generally weak (less than 30% specific 51Cr release) and was abolished by dilutions of antibody 1:1000 or greater. Effector cells were not active when nonimmune serum was substituted for immune serum. Peritoneal exudate macrophages used as controls exhibited higher levels of release and were active with antibody diluted greater than 1:1000. HSV antibody reactive in ADCC appeared 7 days after intrastromal injection of infectious virus. Lymphocyte ADCC activity obtained from draining lymph nodes of infected animals was similar to that obtained with normal animals. Results indicate a weakly active lymphocyte effector-cell system in normal and infected rabbits.