Age-related changes in major lymphocyte subsets were analyzed in 195 cynomolgus monkeys (Macaca fascicularis) aged from one month to 31 years. The percentages of CD20⁺ B cells in peripheral blood lymphocytes (PBL) decreased with age to five years of age, but after that, no significant change was observed. The percentages of CD16⁺ NK cells gradually increased during the first five years and reached the peak at from four to ten years of age, whereas the percentages of CD3⁺ T cells in PBL were relatively constant throughout the life. Among the T cells, the CD4⁺ CD8^- T cells decreased, but CD4^- CD8⁺ T cells increased within the first decade of life. We further analyzed the expressions of CD28 and CD29 molecules on T cells to determine the relation between age-related activation and phenotypic changes. Almost all CD4⁺ CD8^- T cells (>90%) were CD28⁺ at all ages analyzed, but a clear age-related decrease in CD28 expression was demonstrated in CD4^- CD8⁺ T cells during the first ten years. In the case of CD29 expression, age-related increases in CD29^hi cells were apparent in both CD4 ⁺ CD8^- and CD4^- CD8⁺ T cells during the first ten years. The percentages of CD29^hi cells, however, were higher in CD4^- CD8⁺ T cells than in CD4⁺ CD8^- T cells in all ages analyzed. These results indicated that the age-related changes in percentages of major lymphocyte subsets as well as in phenotypes of T cells might be related to the maturation of the immune system including an increase in memory cells in cynomolgus monkeys.