The elimination kinetics of verapamil, an experimental antiarrhythmic agent which inhibits slow-channel activity, were studied in mongrel dogs after i.v. drug administration. The disposition of verapamil follows 1st-order kinetics and may be adequately described by a 1-compartment model. After single i.v. doses of the drug, the overall elimination rate constant (mean .+-. standard error of the mean) was 0.0146 .+-. 0.0021 min-1; the apparent volume of distribution was 4.47 .+-. 0.40 l/kg; and the total body drug clearance was 1244 .+-. 113.4 ml/min. After longer i.v. infusions, the disposition kinetics were similar to those found with bolus dosing. A linear relationship was found between verapamil plasma concentrations and changes in atrioventricular conduction time, as estimated from the P-R interval of the surface ECG (r = 0.95, P < .001). No changes were seen in the QRS duration or Q-T interval. The effect of verapamil on slow-channel-dependent conduction in the heart is directly related to the concentration of the drug in plasma.