Work over the last decades has led to the identification of the factors that influence the survival and homeostasis of conventional T cells. IL-7 and TCR signaling promote the survival of naive CD4(+) and CD8(+) T cells in lymphoreplete mice and their proliferation in a lymphopenic environment, whereas survival and homeostatic proliferation of memory CD4(+) and CD8(+) T cells crucially depend on a combination of IL-7 and IL-15. In contrast, there is little information regarding the factors driving the proliferation of regulatory CD4(+) T cells in response to lymphopenia. In this study, we investigated whether regulatory CD4(+) T cell proliferation in response to lymphopenia was guided by classical homeostatic resources, such as IL-2, IL-7, or TCR-MHC interactions. Altogether, our data suggest that, although homeostatic proliferation of conventional naive CD4(+) T cells is closely related to IL-7 levels, the proliferation of regulatory CD4(+) T cells in response to lymphopenia appears to be primarily controlled by IL-2. The capacity of IL-7 to augment conventional T cell proliferation with minimal concomitant regulatory T cell expansion may be clinically exploitable in the treatment of patients with lymphopenia, especially in the case of chronic viral diseases or cancer immunotherapy.