Two analytical methods are described for the determination of flecainide in serum by high-performance liquid chromatography employing spectrofluorimetric detection. One method concerns total flecainide, whereas the other covers the assay of flecainide enantiomers separately. The stereo-specific assay is based on a precolumn derivatization of flecainide enantiomers to urea derivatives with the chiral compound R-( + )-1 phenyl-ethyl-iso-cyanate. By formation of the permanent diastereomers, the racemic mixture can be resolved with a traditional reversed-phase column. The run time of the total flecainide assay is 15 min, whereas that of its enantiomers is 20 min. The extraction recovery from serum in both methods is 85%. The intraassay precision of the nonstereospecific assay in serum ranged from 99 \pm 3% (coefficient of variation) to 101 \pm 5%. The accuracy of the estimation in serum ranged from 100 to 103%. The intraassay precision of the stereospecific assay in serum ranged from 98 \pm 5% (coefficient of variation) to 103 \pm 7%. The accuracy of the estimation in serum ranged from 101 to 104%. The limit of quantitation was 0.05 mg/L for both methods.