Predictors of a successful outcome of serial electrophysiologic (EP) and drug studies have been identified from among baseline patient characteristics but not from among measures of baseline and drug-related EP effects. Identifying such predictors would be useful in explaining the mechanism of successful drug therapy and in guiding drug development and selection. We prospectively studied EP characteristics in 159 trials in 62 patients with ventricular tachycardia or ventricular fibrillation during antiarrhythmic therapy and compared EP measures between successful (n = 30) and failed trials (n = 129). The average age of the patients was 64 years (range 27 to 78 years); 82% were men and 18% women; and 87% had coronary artery disease. Measurements included R-R, QRS, and QT intervals during intrinsic rhythm and during pacing at cycle lengths of 600 of 400 msec; ventricular effective refractory periods (ERP) during pacing at cycle lengths of 600 and 400 msec; and changes in these measures, comparing treatment with drug-free baseline. Univariate predictors of success (in order of significance) included ERP600/QRS600, sotalol versus other drugs, ERP400/QRS400, delta ERP600, delta R-R, ERP600, QRS400 (negative association), delta ERP400, QRS600 (negative association), ERP400 (all p < 0.1). In two separate multivariate models, one for each drive cycle length, only the ratio ERP600/QRS600 (p = 0.01) in the first model and ERP400/QRS400 (p = 0.01) in the second model were significantly and independently associated with achieving noninducibility with drug therapy. Therefore measures of greater refractoriness and lesser delays in conduction velocity (ie, greater "wavelength") relate to drug success.(ABSTRACT TRUNCATED AT 250 WORDS)