Experiments were designed to determine immunological mechanisms responsible for controlling dissemination of feline rhinotracheitis virus in feline cell cultures. Virus infected cells could be destroyed by three mechanisms--antibody and complement mediated lysis, direct lymphocyte cytotoxicity and antibody dependent cell-mediated cytotoxicity. This latter immune parameter was mediated by both lymphocytes and macrophages and varied in extent in different cats. To ascertain the potential importance of the immunological parameters in curtailing viral spread, the time when virus infected cells could be destroyed by each component was related to the chronological events of viral replication and dissemination. Intracellular infectious virus and intracellular spread occurred at six to seven hours postinfection and extracellular spread at nine to ten hours postinfection. Antibody complement lysis and antibody dependent cell-mediated cytotoxicity occurred at six hours postinfection and direct cytotoxicity at eight hours postinfection. The relevance that these findings might have in relation to the occurrence and frequency of recrudescent disease is discussed.