A simple high-performance liquid chromatographic method has been developed for the measurement of the antiarrhythmic drug amiodarone in small (200 microliter) volumes of plasma or serum. After addition of 2 mole/l phosphate solution, pH 4.5 (20 microliter), containing the internal standard, the sample is vortex-mixed with diisopropyl ether (200 microliter) for 30 sec. A portion (100 microliter) of the resulting extract is analysed on a microparticulate (5 micron) silica column using methanol-diethyl ether (85:15) containing perchloric acid (0.02% v/v) as the mobile phase, and the absorption of the column effluent is monitored at 240 nm. No endogenous sources of interference have been observed, and interference from other drugs is minimal. The procedure is rapid, an analysis in duplicate taking less than 15 min to complete. The limit of sensitivity of the assay is 0.05 mg/l, and the concentrations of amiodarone measured in plasma samples from patients under treatment with this compound ranged from 0.15 to 4.5 mg/l.