So far no comparative studies have been conducted to know whether physiological influences related to sex hormonal differences affect the age-related changes of the immune system. The aim of this study was to investigate whether pregnancies and sex influence the age-related changes in the peripheral lymphoid compartment and functions of T cells in mice. Using flow cytometry, we examined changes in (Thy1.2+) T cells, (B220+) B cells and (CD11b/Mac-1+) macrophages in the spleen of multiparous and virgin females and males at 2, 8, 15 and 23 months of age. The development of naive (CD44low) and memory (CD44high) cells were investigated in CD4+ and CD8+ T cell subsets. To analyze the age-related changes in functions of T cells, we examined the secretion of some T cell immunoregulatory cytokines (IL-2, IL-4, gamma-interferon and GM-CSF) of in vitro Concanavalin A-activated spleen cells of C57BL/6 mice. Both short term (8 months) and long term (15-23 months) effects of pregnancies were obvious in the age-related changes of the immune system. Short term effect included delayed appearance of memory CD4+ cells and the preserved IL-2 production. At eight months, shortly after pregnancies, both parameters were higher in multiparous females. Later effects of pregnancies were evidenced by a higher level of macrophages (Mac-1+) than in other groups throughout life. The increased gamma-interferon, IL-4 and GM-CSF productions appeared earlier, at 15 months, IL-4 and GM-CSF levels remained higher in multiparous females than in virgin females and males in late adulthood. Sex differences were also noticed: males exhibited lower macrophage levels after one year and gamma-interferon secretion capacity than females in late life. This study underlines that the onset, magnitude and kinetics of the age-related changes in the distribution of immune cells and T cell functions are parity- and sex-dependent. These changes may influence the incidence of age-related diseases and may explain the greater longevity of women, especially the multiparous ones.