In order to evaluate the electrophysiological effects of the combined administration of disopyramide and mexiletine on anterograde accessory pathway conduction, we studied 11 patients with Wolff-Parkinson-White (WPW) syndrome. Disopyramide was first infused intravenously at 1 mg kg-1 for 5 min followed by a continuous infusion at 0.025 mg kg-1 min-1. After the infusion rate of disopyramide was decreased to 0.004 mg kg-1 min-1 to maintain a lower serum concentration, mexiletine was infused at 2 mg kg-1 for 5 min followed by a continuous infusion at 0.008 mg kg-1 min-1 (protocol 1). The shortest atrial paced cycle length with 1:1 anterograde accessory pathway conduction (shortest CL with 1:1) and the anterograde effective refractory period of the accessory pathway (ERP) were measured: (1) before drug administration, (2) after disopyramide was given alone, and (3) after disopyramide and mexiletine were combined at lower concentrations. The same protocol was repeated with the order of drug administration reversed (mexiletine followed by disopyramide) in all patients (protocol 2). Both disopyramide and mexiletine lengthened the shortest CL with 1:1 and the ERP to the same degree. The combination of disopyramide and mexiletine at lower concentrations further lengthened the shortest CL with 1:1. It was longer than with disopyramide (protocol 1) or mexiletine (protocol 2) alone [protocol 1: 412 +/- 169 ms (combination) vs 356 +/- 117 ms (disopyramide); P less than 0.05, protocol 2: 409 +/- 166 ms (combination) vs 355 +/- 119 ms (mexiletine); P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)