Hypertonic sodium bicarbonate (HSB) has been reported to reduce the toxicity of Class IC antiarrhythmic agents in rats and, anecdotally, in patients. A pilot study was conducted of the safety and efficacy of HSB for reversing the electrocardiographic effects of therapeutic doses of encainide or flecainide in ten patients taking these drugs for chronic ventricular arrhythmias. Patients had a mean drug-induced QRS prolongation before treatment of 27.6 +/- 8.8%. Each patient received a single dose of HSB 100 mEq or normal saline IV over 5 minutes on two separate occasions. The administration of treatments was blinded and balanced. There were no important side effects of HSB. Venous blood pH, CO2 content and sodium concentration were all significantly increased by HSB in comparison to saline. No differences were found during the 2-hour observation period in the primary endpoint, QRS duration, the PR or QT intervals, or the frequency of premature ventricular beats. It was concluded that HSB 100 mEq does not reduce QRS duration in patients taking therapeutic doses of flecainide or encainide. Because HSB was well tolerated, investigation of its use in higher doses or in patients with overt toxicity due to Class IC drugs is feasible.