This study was aimed at analysing rapamycin (RAPA) rescue therapy with calcineurin inhibitor (CNI) withdrawal in renal transplant patients primarily presenting with CNI-nephrotoxicity (CNI-Neph), chronic allograft nephropathy (CAN) without [CAN(a)] and with histological changes suggestive of chronic rejection [CAN(b)]. In 36 patient with CNI-Neph (n = 6), CAN(b) (n = 21), CAN(a) (n = 7), and others (n = 2) RAPA therapy was started 4.4-115 months (median 30.6 months) after renal transplantation. During a follow up of 3-33 months (median 19 months) parameters of kidney function were recorded. Three patients on haemodialysis did not show any recovery of graft function. Of the remaining 33 patients renal function improved in 22 (66.7%), was stable in three (9%) but deteriorated in eight (24%) patients, of whom seven (21%) required haemodialysis thereafter. Success rate of RAPA therapy differed with respect to the histological diagnosis: 70% in CAN(b), 80% in CNI-Neph and 33% in CAN(a). Furthermore, in patients with creatinine levels above 400 mum (n = 6) graft function rarely improved (n = 2, 33%). The RAPA rescue therapy with CNI withdrawal appears promising in a special cohort of patients with chronic renal allograft dysfunction even late after transplantation.