A sensitive, specific, high-pressure liquid chromatographic assay for the determination of tocainide in whole blood is described. The residue from a methylene chloride extract of alkalinized blood was resolvated in a mobile phase of methanol--water (47:53) containing 1% acetic acid and 6.16 mM 1-octanesulfonic acid, adjusted to pH 4.0. Chromatography was performed on a reversed-phase column with detection at 254 or 225 nm. The limits of accurate measurement were 2 microgram/ml for a 1-ml blood sample monitored at 254 nm and 0.2 microgram/ml for a 2-ml sample monitored at 225 nm. The assay was tested on samples from emergency protocol patients and was also found suitable for single-dose pharmacokinetic studies.