We compared the degrees of depletion and the rates of recovery of CD4+ T cells in young and old mice given a single injection of an anti-CD4 (GK1.5) mAb. We found that in young mice the CD4+ population of T cells was completely depleted from the peripheral blood and, subsequently, the lymph nodes and spleen. Young mice recovered 80% of CD4+ T cells within 100 days after the injection. Although aged mice have less CD4+ T cells, CD4+ T cells were depleted by only 60% after mAb injection. This finding was associated with prolonged circulation of Ab-coated T cells. The rate of repopulation of peripheral CD4+ T cells was also affected by aging, because 5 times less CD4+ T cells appear in aged than in young mice between days 14 and 100 post injection. Further, we found that the CD4+ T cells that are depleted in both young and old mice by injection of anti-CD4 mAb are CD45RBhigh, suggesting a preferential depletion of immature cells. Finally, the thymus appears to be required to repopulate the T cell population post injection, because thymectomized young mice failed to recover CD3+CD4+ cells.