Immunosenescence occurs with aging, which is seen in decline in response to mitogens PHA, ConA, decline in cell-mediated immunity, increase in anemia, and increase in autoimmune antibodies to erythrocytes and DNA. These studies compared FTS, TP5, TM4, and TF5 in C57BL/6NNia mice. Mice aged 4, 26, 52, 78 and 104 wk were treated with various hormones 5x/wk for 3 wk and monitored for hormonal effects on weight; hematocrit; peripheral blood, spleen, and thymic cell numbers; spleen and peripheral blood cell mitogen responses to PHA, ConA, LPS; IgM hemolysin autoantibody; and cell-mediated cytotoxicity to P815 allogenic cells. Hormone treatments altered mitogen responses, enhanced IgM hemolysin autoantibody production, and modulated cell-mediated immune responses. The effects were not consistent for every hormone. There was a tendency for enhancement in younger mice and suppression in older animals. Treatment with FTS showed the greatest changes in either enhancing or suppressing the different parameters measured. The hormonal effects appeared to be age specific in that certain activities were altered for certain age groups but not in others. Hormone treatment did not restore any immune parameters in old mice to the level of young animals. In general, the different hormones did not consistently produce the same effects in C57BL/6NNia mice of different age groups. Even though all animals received from National Institutes on Aging (NIA) animal models program were held under strictly controlled conditions, intrinsic variations between cohorts of different ages are difficult to control. Cohorts of aging animals tested at different times might be intrinsically different. This inherent variability in the cohorts could affect the range of activity, specificity and reproducibility of hormone effects in vivo. Most importantly, it should be emphasized that cross-sectional data identifies age differences rather than age changes. There is no assurance that age changes in any individual or in all subpopulations follow this pattern. In our studies only healthy animals were used. Old, sick, or tumor-bearing animals were culled out prior to being sent to us. Therefore, the 78- and 104-wk-old mice represent selected healthy cohorts. The age changes that take place can be answered only from repeated measurements made in the same individual over time.