BACKGROUND: Tacrolimus is more diabetogenic than cyclosporine. However, this difference is only discernible in the first few months after renal transplantation. In randomized trials, investigating the effects of immunosuppression after renal transplantation, no increase in diabetes mellitus has been reported. However, no sensitive technique was used in these trials, so subclinical alteration of glucose metabolism cannot be excluded. METHODS: We, therefore, decided to use an intravenous glucose tolerance test (IV-GTT), to investigate whether conversion from cyclosporine-based immunosuppression, with a median trough level of 120 microg/l, to tacrolimus-based immunosuppression with a median trough level of 6.5 microg/l influences glucose metabolism and whether patients on steroids behave differently from those not on steroids. RESULTS: Thirty stable, non-diabetic patients, transplanted 10 or more years earlier, were converted from cyclosporine to tacrolimus without changing their concomitant medication. IV-GTT's were performed before and 2.5 months after the conversion. Before conversion, 40% of the patients had an abnormal glucose disappearance rate (kG): in 7%, kG was below 0.8 (abnormal range) and in 34%, kG was between 0.8 and 1.2 (indeterminate range). After conversion, stimulated insulin production, kG, HbA1C and fasting glucose did not change significantly. Insulin resistance (HOMA-R) of the whole group increased significantly, mainly due to a rise in HOMA-R in patients on steroids (n = 18). None of these patients developed overt diabetes mellitus. CONCLUSIONS: Some 40% of long-term cyclosporine-treated patients had an abnormal glucose metabolism. Conversion from cyclosporine to tacrolimus does not negatively influence stimulated glucose metabolism or insulin resistance in stable, steroid-free renal transplant recipients. However, in patients receiving steroids, conversion leads to an increase in insulin resistance while insulin output remains the same.