OBJECTIVE There is growing evidence of the effects of immunosuppressive agents on "immune targets" in renal transplantation. Immunological monitoring could indirectly measure the suppressive effect of these drugs and guide early preventive interventions in transplant recipients. Due to the selective antiproliferative effect of mycophenolate mofetil (MMF) on lymphocytes, our goal was to determine whether MMF modulates peripheral blood lymphocyte subsets (PBLS) in kidney allograft patients. METHODS We assessed absolute CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD19(+), CD16(+)CD3(-) PBLS counts and CD4/CD8 ratios for 12 months in three groups of kidney allograft patients stratified according to maintenance immunosuppressive regimen: group A (n = 31), which started MMF with prednisone (P) + cyclosporine A (CyA), and two control groups, B (n = 19) and C (n = 15) on P + CyA + azathioprine (Aza) and P + CyA regimens, respectively. We compared intra- and intergroup lymphocyte counts and ratios. RESULTS Intergroup comparisons showed a significant reduction in all PBLS in group A (CD19(+) from 3 months and other subsets from 6 months), whereas there were no significant changes in PBLS in the other group analyses or comparisons. CONCLUSIONS Our findings suggest that (1) MMF modulates all PBLS in kidney allograft patients, causing a progressive reduction occurring earlier in CD19(+), and (2) we can rule out that these changes were caused by the "natural immunological evolution" of the transplantation. These results could offer a new method for immunological monitoring of transplant patients.