The introduction of cyclosporine (CYA) to the immunosuppressive armamentarium has had a significant effect on graft survival. An improvement in the formulation from the oil-based to a microemulsion-based form has resulted in better absorption and more predictable CYA bioavailability. Since the introduction of the first microemulsion form (Neoral), several bioequivalent formulations are now available and are switched in a 1:1 fashion at pharmacies to curtail costs. The purpose of our study was to study the effect of a 1:1 switch from Neoral to Gengraf on CYA trough levels and serum creatinine (SRC) in renal transplant recipients with stable graft function. Eighty-two renal transplant recipients with stable graft function were enrolled in the study, and of these, 73 were switched to Gengraf, whereas nine remained on Neoral. The 13 patients switched to Gengraf required a dosage change after the mean CYA trough levels changed from 234 +/- 96 ng/mL at baseline to 289 +/- 102 ng/mL (p < 0.05) at 2 wk. With the adjustments in dosage, the levels approached the baseline trough concentrations (239 +/- 151 ng/dL). The nine patients who remained on Neoral had no change in the CYA levels or SCR. Nearly 20% of patients who switched to a bioequivalent CYA preparation required a dose adjustment to return to pre-conversion CYA trough levels. Our study raises serious concerns regarding the switchability of generic CYA for Neoral without careful follow-up therapeutic drug monitoring.