A sensitive and selective gas chromatographic (GC) method for the quantitation of flecainide acetate, a new antiarrhythmic agent, was developed. The unchanged drug and internal standard were separated from biological fluids by a sequence of solvent extractions and then the drug was derivatized. The pentafluorobenzamide derivatives were chromatographed on a 3% SP-2250 glass column and detected with a nickel-63 electron-capture detector. By this method, greater than or equal to 12.5 ng of flecainide/mL can be quantitated in a 1-mL sample of plasma, saliva, or urine. The intraday precision, expressed as the RSD, at plasma levels of 12.5, 25, 50, 100, 200, 300, 400, and 600 ng/mL was 3.4, 6.2, 5.3, 6.4, 1.0, 1.6, 2.0, and 0.5%, respectively; the accuracy, expressed as relative error at these levels was -24.6, -6.9, -6.0, +0.6, +3.8, -0.3, +2.4, and -1.4%, respectively. The interday precision at these levels was 13.8, 13.0, 5.7, 7.6, 8.3, 6.1, 9.0, and 5.4%, respectively. Several other antiarrhythmic agents and one beta-blocker, which might be administered concurrently with flecainide acetate, do not interfere with the assay.