Delayed addition of azathioprine (Aza) to an ongoing cyclosporine-prednisone protocol was started 11.3 +/- 9.9 months after renal transplantation in 31 patients. Group I (n = 10) had chronic renal function deterioration due to chronic rejection, group II (n = 11) had repeated or severe acute rejection episodes and group III (n = 10) had cyclosporine (Cs) toxicity despite drug tapering. In group I, SCr had risen over the 6 months prior to Aza addition (P < 0.05), renal function declining at a rate of -0.13 +/- 0.12 SCr(-1). In the 6 months post-Aza, renal function improved at a rate of 0.05 +/- 0.07 SCr(-1), and during the entire follow-up at a rate of 0.05 +/- 0.12 SCr(-1) (P < 0.01) with stable Cs levels. In group II the decline in renal function was greater, though the rate of decline was stopped after Aza. In group III, renal function improved in eight patients. After 23 +/- 12 months of follow-up, 15 patients had improved graft function, two were stable, 12 had worsened (nine on dialysis) and two had died. Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to Cs-prednisone-treated renal allograft patients with chronic rejection or Cs toxicity, with long-term beneficial effects in a high proportion of patients.