Transgenic (TG) mice expressing a high copy number of interleukin (IL)-7 cDNA under the control of the major histocomaptability complex (MHC) class II promoter display a 10–20-fold increase in total T cell numbers. Here, we show that the increase in T cell numbers in IL-7 TG mice is most apparent at the level of memory phenotype CD44^hi CD122^hi CD8⁺ cells. Based on studies with T cell receptor (TCR) TG mice crossed to IL-7 TG mice, increased levels of IL-7 may provide costimulation for TCR recognition of self-MHC ligands and thus cause naive CD8⁺ cells to proliferate and differentiate into memory phenotype cells. In addition, a marked increase in CD44^hi CD122^hi CD8⁺ cells was found in IL-7 TG IL-15⁻ mice. Since these cell are rare in normal IL-15⁻ mice, the dependency of memory phenotype CD8⁺ cells on IL-15 can be overcome by overexpression of IL-7.