The characteristics of the Abbott selective fluorescence polarization immunoassay for cyclosporine in whole blood (TDXSP) were compared with the Incstar radioimmunoassay by using kit standards (INCSP) or TDXSP standards (INCTDX) with samples from adult (48) and pediatric (24) liver-transplant recipients and a further 32 control specimens. The TDXSP assay was faster, less labor intensive, and more precise at higher concentrations; it gave results a median of 5 micrograms/L lower than INCSP values, irrespective of biliary T-tube status, patient's age, or severity of cholestasis in nine patients, comparisons being made for serum bilirubin more than eight times normal or less than 50 mumol/L. However, both assays overestimated INCTDX values by approximately 10%. There was a progressive increase in the ratio of TDXSP to both INCSP and INCTDX results in 57 samples stratified in relation to serum bilirubin concentrations. Cross-reactivity of TDXSP with cyclosporine metabolites M1 (23%) or M17 (12%) was greater than for INCSP (15% and 5%, respectively) or INCTDX (22% and 4%, respectively), but the converse was true with M21 (2% for TDXSP vs 4% and 8%, respectively). Some overestimation of cyclosporine whole-blood concentrations (relative to INCTDX results) may be detected with either the TDXSP (because of cross-reactivity with metabolites) or the INCSP assays (probably because of matrix effects). The similar magnitude of these overestimations suggests that alternative factors such as speed, precision, and cost may influence which method one selects for use in routine monitoring.