Studies demonstrated that deficiency in 17-estradiol (E-2) in postmenopausal women influences their immune system. However, few studies have reported alterations in immunologic presentation during nonnatural menopause in young females. Here we compared the differences in immune response between young C57BL/6N mice with surgical or medical variectomy and aged C57BL/6N mice with the common feature of E-2 deficiency following Con A stimulation. We observed inverted CD4/CD8 ratios in the aged group and apparent reduced production of serum immunoglobin (Ig)G, IgA, and IgM in the surgical group, whereas changes in immune parameters in the medical group were moderate. These data suggested that the immunological response to Con A stimulus differed among the three groups and that E-2 deficiency was only partially responsible for the development of immune deficiency in aged mice.