Background: Decline in immune function has been reported to predictably accompany advancing age. However, to our knowledge, few studies have specifically characterized the rapidly expanding advanced elderly population or controlled adequately for concurrent diseases. Objective: To assess whether successfully reaching an advanced age in good health is associated with preserved immune function. Methods: We prospectively compared in vivo with in vitro variables of immune function in 29 healthy, independently living elderly subjects (mean age, 80 years; age range, 75-103 years) and in 21 healthy young control subjects (mean age, 29 years; age range, 25-35 years) in a Veterans Affairs Medical Center. Results: In vivo, among elderly and young subjects, numbers of total white blood cells, monocytes, lymphocytes, and lymphocyte subsets (CD4+ and CD8+ T lymphocytes and CD20+ B cells) were similar, as were levels of total serum IgG and IgM. Only levels of serum IgA were higher in the elderly subjects (3.0 vs 1.7 g/L; P=.001). Functionally, both groups showed vigorous responses to protein (tetanus and diphtheria toxoids) and polysaccharide (23-valent pneumococcal) vaccines. Although levels varied, the fold increases in vaccine antigen-specific IgG were not significantly different in young and elderly subjects, and the avidities of IgG to pneumococcal polysaccharides 14 and 19F were similar before and after vaccination. In vitro, proliferative responses of blood mononuclear cells to T-lymphocyte and B-cell mitogens (pokeweed mitogen, Staphylococcus aureus Cowan strain I, and S aureus Cowan strain I plus interleukin 2), and lipopolysaccharide-induced production of tumor necrosis factor α, were comparable in elderly vs young subjects. Conclusion: Successful aging, defined by reaching an advanced age with one's overall health intact, may be associated with preserved immune function and adequate responses to vaccines.