BACKGROUND Variability in cyclosporine drug exposure of > or = 20% has been shown to be a risk factor for the development of chronic renal allograft rejection. We tested the hypothesis that a cyclosporine microemulsion (CsA-ME) would result in reduced variability in stable maintenance renal transplant patients when compared with the original formulation of cyclosporine (CsA). METHODS The 31 maintenance renal transplant recipients were part of a multicenter, randomized, double-blind, prospective study comparing the CsA formulation with the CsA-ME formulation. Pharmacokinetics analyses were performed at two centers 1, 4, 12, and 52 weeks after patients were randomized to continue receiving CsA or to convert to CsA-ME. RESULTS The means of the week 1-, 4-, and 12-week areas under the concentration-time curves (AUC), and Cmax were significantly higher and the Tmax was significantly shorter in those patients converted to CsA-ME than in those remaining on CsA. There was no correlation between change in AUC after conversion and change in serum creatinine. The coefficient of variation values for dose-adjusted AUC, expressed as a percentage (%CVAUC), were lower in CsA-ME patients than CsA patients after both 12 and 52 weeks. Over the initial 12 weeks. %CVAUC values of < or = 20% were seen in a significantly greater proportion of CsA-ME patients than CsA patients. CONCLUSIONS Conversion of maintenance renal transplant recipients from CsA to CsA-ME resulted in improved absorption of cyclosporine. The CsA-ME formulation resulted in long-term reduction in the variability of cyclosporine exposure and more consistent pharmacokinetics.