Ketoconazole (KET) is frequently used as a cyclosporine (CyA)-sparing agent. Adequate exposure to CyA is critical to avoid acute rejection (AR) or chronic rejection (CR). We compared the pharmacokinetic profiles of nine stable renal transplant patients on CyA before and after conversion to KET (200 mg/d of KET simultaneous with CyA). The CyA doses were adjusted to achieve similar drug exposures. The mean dose reduction of CyA while on KET was 83% from 3.2 +/- 0.9 to 0.6 +/- 0.2 (P <.000). Addition of KET produced a significant decrease in the absorption parameters of CyA and an increased elimination half-life. Coefficient of variation (CV) of AUC was significantly increased. Serum creatinine (SCr) at 3 months after switch remained the same. One patient experienced a grade I AR episode (11%). There were no adverse effects related to KET. Although addition of KET to CyA can significantly decrease the CyA dose, the observed pharmacokinetic changes involved decreased absorption and increased CV, which may respectively relate to AR and CR. The 11% AR rate observed is of concern. We do not recommend switching patients to KET as this may imply an increased risk of late AR or CR.