Viruses have developed various strategies to coexist with vertebrate hosts. Lactate dehydrogenase-elevating virus (LDV) is a highly cytopathic virus exhibiting an extraordinary rate of replication; LDV nevertheless establishes a persistent infection without harming the host. The cytotoxic and helper T cell responses to LDV were monitored in mice with different genetic backgrounds. LDV-specific cytotoxic and helper T cells were found in all strains tested. These responses persisted for at least up to 250 days despite high levels of LDV in the blood. Thus, the cytopathic LDV induces and maintains an inefficient immune response that is not exhausted. LDV infection in mice reveals a special type of host-virus equilibrium where LDV quickly establishes persistence despite continuously induced LDV-specific helper and cytotoxic T cell responses, which apparently are too slow to control the highly cytopathic and extremely fast replicating virus.