Previous studies established that retrovirally infected young mice produced large amounts of autoantibodies to certain T-cell receptor (TCR) peptides whose administration diminished retrovirus-induced immune abnormalities. C57BL/6 young (4 weeks) and old (16 months) female mice were injected with these same synthetic human TCR Vβ.1 or 5.2 peptides. Administration of these autoantigenic peptides to old mice prevent immunosenesence, such as age-related reduction in splenocyte proliferation and interleukin-2 (IL-2) secretion. TCR Vβ peptide injection into young mice had no effect on T- or B-cell mitogenesis and IL-4 production while modifying tumour necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ) secreted by mitogen-stimulated spleen cells. TCR Vβ injection also retarded the excessive production of IL-4, IL-6 and TNF-α induced by ageing. These data suggest that immune dysfunction and abnormal cytokine production, induced by the ageing process, were largely prevented by injection of selected TCR Vβ CDR1 peptides.