Simian immunodeficiency virus (SIV) infects a small number of CD4+ T cells including "memory" T cells. The following describes the cell surface markers which may delineate subsets of CD4+ memory T cells and reviews how memory CD4+ T cells are activated and regulated through the T-cell receptor and such accessory receptors as CD28. The factors which may influence initial expression and infection of T cells by CD4 are discussed. Unlike activated and infected T cells, unstimulated CD4+ T cells have little or no SIV DNA detectable in the genomic fraction, but key activation signals may promote integration of viral DNA in memory T cells. Bacterial superantigens (SuperAg) can promote increased levels of SIV viral DNA in mature and immature T cells. Immunodeficiency virus products such as gp120, Nef, and Tat can affect CD4+ T-cell function. Whereas Nef can reduce expression of CD4, Tat reduces the expression of CD28. We hypothesize that the lack of expression of key accessory molecules on CD4 lineage T cells infected with immunodeficiency viruses may make infected T cells more susceptible to recall-antigen-induced programmed cell death.