A longitudinal study of peripheral blood lymphocyte subsets was performed in 23 renal allograft recipients treated with prophylactic antilymphocyte antibodies, CsA, and steroids. At day 0 samples were obtained before transplantation (Tx), and afterwards at months +1, +3, +6, +9, +12, +24, +36, and +48. In all patients, after the depletion of lymphoid subsets during antilymphocyte antibody treatment, CD8+ lymphocytes recovered and reached higher values than those observed prior to Tx. This was mainly due to an increase in CD8+CD45RA+ lymphocytes; in contrast, the levels of "memory" CD4+ T cells and the CD4+CD62L+ subset remained low during all the follow-up period. In patients with preserved graft function (n=14) (with creatinine levels below 200 micromol/mL), the initial, relative decrease in CD4+ T cells was never reversed and the recovery of CD8+ lymphocytes started early. They also presented a peak of HLA-DR antigen expression at 1 month, not observed in those patients displaying a suboptimal graft function. At 1 month, the patients with suboptimal graft function (n=9) (with creatinine levels above 200 micromol/mL) showed higher number of CD4+ T cells, delayed recovery of CD8+ lymphocytes, and higher percentage of activated lymphocytes from month +3 on than well-functioning kidney recipients. Both CD8+ lymphocytes and HLA-DR+ T cells, found at month + 1 post-Tx, were negatively correlated with the concentration of creatinine along the follow-up. Interestingly, the mean percentage of CD4+CD25+ T cells found 36 and 48 months after Tx were positively correlated with creatinine concentration at these times. These findings indicate that variations in the distribution of lymphocyte subsets are related with a long-term graft outcome. Within the first month after Tx, a rapid recovery of CD8+ lymphocytes, but not of CD4+ T cells, and a peak of HLA-DR expression, are associated with a good graft function. In contrast, long-term expression of activation markers is related with renal dysfunction.