Phenotypic characterization of T and B lymphocytes allows the discrimination of functionally different subsets. Here, we questioned whether changes in peripheral lymphocyte subset distribution reflect specific clinical and histopathological entities after renal transplantation. Sixty-five renal transplant recipients with either histologically proven (sub)clinical acute rejection or chronic allograft dysfunction, or without abnormalities were studied for their peripheral lymphocyte subset composition and compared with 15 healthy control individuals. Naive, memory and effector CD8+ T-cell counts were measured by staining for CD27, CD28 and CD45RO/RA. In addition, we studied the CD25+ CD4+ T-cell population for its composition regarding regulatory Foxp3+ CD45RO+ CD127– cells and activated CD45RO+ CD127+ cells. Naive, non-switched and switched memory B cells were defined by staining for IgD and CD27. We found a severe decrease in circulating effector-type CD8+ T cells in recipients with chronic allograft dysfunction at 5 years after transplantation. Percentages of circulating CD25+ CD127low CD4+ regulatory T cells after transplantation were reduced, but we could not detect any change in the percentage of CD127+ CD45RO+ CD4+ activated T cells in patients at any time or condition after renal transplantation. Regardless of clinical events, all renal transplant recipients showed decreased total B-cell counts and a more differentiated circulating B-cell pool than healthy individuals. The changes in lymphocyte subset distribution probably reflect the chronic antigenic stimulation that occurs in these transplant recipients. To determine the usefulness of lymphocyte subset-typing in clinical practice, large cohort studies are necessary.