Aging is associated with a progressive decline in T cell-mediated immune responses. Little is known about the effect of aging on antigen presenting cells (APC). We have recently reported an age-related decline in proliferative response of peripheral blood mononuclear cells from elderly volunteers to Staphylococcus enterotoxin B (SEB). Since SEB-induced stimulation of T cells is not restricted by major histocompatibility complex, experiments were conducted in which T cells and APC from young and healthy elderly subjects were combined. We initially demonstrated the decreased SEB-induced proliferative capacity of elderly T cell elderly APC co-cultures when compared with young T cell young APC co-cultures. Combination of purified T cells from elderly donors with APC from young donors maintained a reduced T cell proliferative response. Age-related decline in T cell function was also established by the reduced proliferative capacity of elderly T cells co-cultured with a reference monocyte cell line. Surprisingly, co-culture of APC from healthy elderly donors with purified T cells from young donors enhanced T cell proliferation. APC from elderly donors also marginally enhanced the proliferative response of an SEB-specific T cell line.