Summary: The method of measurement of cyclosporine concentrations in renal transplant recipients varies between centers and employs either high-performance liquid chromatography (HPLC) or radioimmunoassay (RIA). The merit of using HPLC for identifying the parent compound versus the RIA technique, which also measures certain cross-reactive metabolites that accumulate during renal impairment, is controversial. As a result of the lack of uniformity among centers, an abundance of complex literature that describes the disposition of this potent immunosuppressive agent, as well as a wide range of guidelines for therapeutic monitoring, has evolved. To examine the influence of assay methodology on the repeated determination of cyclosporine in the immediate postoperative period, a time when renal function is often unstable, eight renal transplant recipients were studied after i.v. and oral administration on up to four separate occasions. Whole-blood samples were analyzed by HPLC and RIA. Intravenous kinetic analysis yielded a mean total body clearance of 0.24 \pm 0.2 L/min (RIA) and 0.31 \pm 0.1 L/min (HPLC) (p > 0.05), the mean volume of distribution was 2.17 \pm 0.6 L/kg (RIA) and 2.75 \pm 1.2L/kg (HPLC) (p > 0.05), and a mean half-life was 11.7 \pm 4.4 h (RIA) and 12.8 \pm 3.8 h (HPLC) (p > 0.05). The mean bioavailability was 0.36 \pm 0.23 (RIA) and 0.28 \pm 0.15 (HPLC) (p > 0.05). Regression of the 12-h cyclosporine (RIA versus HPLC) concentration yielded a line described by the following equation: RIA = 72 + 1.6 (HPLC). The mean ratios (RIA/HPLC) of the area under the blood cyclosporine concentration versus the time curve (AUC) were 1.6, 1.5, and 1.7 during the oral study periods and were poorly correlated with the serum cre-atinine level. Overall, the two assay methods provided similar pharmacokinetic parameter estimates. However, correlation between the 12-h cyclosporine level determined by RIA and the AUC by HPLC yielded an overestimation of the 24-h AUC determined by HPLC and indicates that therapeutic monitoring of the parent drug in the immediate postoperative period may best be accomplished by HPLC analysis.