The relationship between specific T cell subset alterations and mortality has not been well characterized in older adults. The specific aim was to determine whether specific T cell subsets are associated with an increased risk of death. We conducted a case-control study of T cell subsets (CD4+ and CD8+ T cells, and subsets of these cells defined by expression or non-expression of CD28, CD45RA, and CD45RO) nested within two complementary prospective cohorts of women aged 65 and over living in the community, the Women's Health and Aging Studies (WHAS). Cases consisted of 61 women who died during 5 years of follow-up, and controls consisted of 61 women matched by age, frailty, and morbidities who survived during 7 years of follow-up. There were no significant differences between cases and controls in any of the T cell subsets studied. When analyses were stratified by frailty status, these data suggest that CD8+CD28- lymphocyte counts were significantly higher among women who were frail compared with pre-frail and non-frail women.