The Friend retroviral (FV) model is used here to investigate the role of CD4 T (Th) cells in recovery from acute FV infection. Depletion of Th cells in high recovery mice leads to fatal erythroleukemia owing to high viral load. CD8 T-cell dependent early recovery from FV infection is Th cell-independent but long-term maintenance of effector and memory CD8 T cells requires Th cell help. Moreover, Th cell help is essential for production of neutralizing antibodies by B cells in response to FV. The peak FV-specific Th cell responses is far greater in magnitude in high recovery mice than intermediate recovery mice, which differ in their MHC-II background. Effector Th cells are able to produce anti-viral IFN-¿ to reduce viral load only until 3 weeks post infection and subsequently lose their anti-viral effector functions due to the presence of Regulatory T (Treg) cells. Depletion of Treg cells increases the frequency of IFN-¿ producing FV-specific Th cells and decreases the viral load further in the infected mice. Considered together, our findings imply that therapeutic manipulation of Treg / Th - cell number and/or function could improve immune control of retroviral infections.