The Abbott TDx fluorescence polarization immunoassay was evaluated for the determination of serum digoxin concentrations. Within-assay precision was less than 4% coefficient of variation (CV) for concentrations ranging from 0.64 to 3.75 ng/mL. Between-assay precision was 14.5% CV at 0.75 ng/mL, 5.7% CV at 1.50 ng/mL, and 4.9% CV at 3.48 ng/mL. Sensitivity to 0.2 ng/mL digoxin was confirmed. Correlation of 86 patient specimens assayed by radioimmunoassay (RIA) with the TDx showed the following: correlation coefficient r = 0.94, slope = 0.93, intercept = 0.11, and Sy/x = 0.19. Recovery from serum at concentrations of 0.97 ng/mL and 4.50 ng/mL averaged 98%. No significant interference from lipemia, icteria, or hemolysis was observed. Spironolactone showed no cross-reactivity with the antibody, while digitoxin exhibited significant cross-reactivity. Compared to the RIA procedure, the TDx assay was more rapid, reliable and, in this clinical situation, more cost effective.