The analytical performance of specific and nonspecific fluorescence polarization immunoassays (FPIAs, Abbott Laboratories) for cyclosporine was compared. Both specific and nonspecific FPIAs demonstrated excellent between-run coefficients of variation (5.9% vs. 3.9%) at three levels of control, and a high degree of between-center reproducibility (r2> 0.96). In addition, the correlation between cyclosporine levels measured by specific and nonspecific FPIAs was statistically significant, though imperfect, in both renal (r2= 0.70) and cardiac transplant patients (r2= 0.55). In kidney transplant patients, the nonspecific/specific ratio was significantly higher in patients with serum bilirubin concentration exceeding 3 mg/dl (5.9 ± 2.6 vs. 2.8 ± 1.1), due to impaired elimination of cyclosporine metabolites in the bile. The nonspecific/specific ratio was also significantly higher in heart transplant patients early (<1 month) posttransplant compared with patients in the late posttransplant period (3.4 ± 0.8 vs. 2.9 ± 0.8). The Abbott FPIA provides a highly precise method for measuring cyclosporine, with a turnaround time of 15–20 min. The specific monoclonal FPIA has the additional advantage of measuring primarily unchanged cyclosporine and thus has an imperfect correlation with the nonspecific polyclonal FPIA. Together with clinical data, the use of FPIAs may help to improve the efficiency of cyclosporine therapeutic drug monitoring.