Abstract: The effects of six antiarrhythmic drugs on transient outward current(I_to) in rat ventricular myocytes were examined by using the patch clamp whole cell recording technique. Quinidine, nifedipine, and imipramine resulted in a concentration dependent inhibition of I_to with IC₅₀ s of 5.4, 10.9 and 6.0 μmol·L^-1, respectively. All three agents produced a concentration dependent increase in the rate of inactivation of I_to. Disopyramide, procainamide and E-4031 produced little inhibition of I_to even when present at 100 μmol·L^-1. The results from this study show that quinidine, nifedipine and imipramine are potent inhibitors of I_to and that inhibition is mediated through preferential interaction with the open channel.