As class I drugs often fail to control ventricular tachycardia when used individually, two such drugs may be combined in an attempt to increase efficacy. The effect of combinations of class I drugs was tested in nine patients undergoing electrophysiologic study for documented ventricular tachycardia or fibrillation, in whom single class I drugs failed to prevent the induction of sustained ventricular tachycardia. By study design, all patients had inducible ventricular tachycardia during the control study, after receiving intravenous procainamide, 1306 ± 243 mg alone, oral quinidine, 1600 ± 0 mg alone, and in five patients, oral disopyramide, 1200 ± 0 mg alone. After oral quinidine and (on a subsequent day) oral disopyramide were found to be ineffective, intravenous procainamide was added and the study was repeated. All patients continued to have inducible sustained ventricular tachycardia despite the addition of procainamide. All showed an increase in tachycardia cycle length; quinidine alone vs qunidine plus procainamide, 351 ± 61 vs 499 ± 65 msec, p < 0.0005; disopyramide alone vs disopyramide plus procainamide, 405 ± 41 vs 494 ± 31 msec, p < 0.005. Also, induction of tachycardia was easier on the combination in 9 of 13 tests where this could be assessed (five of eight patients on quinidine plus procainamide and four of five patients on disopyramide plus procainamide). In conclusion, although induced ventricular tachycardia was slower on two class I drugs and therefore might be better tolerated, in no patient did the combination prevent induction of sustained tachycardia. Easier induction suggests that spontaneous episodes might become more frequent. Therefore such combinations cannot be expected to provide effective prophylaxis in patients refractory to large doses of individual class I drugs.