The interaction between dl-sotalol and isoproterenol on the ventricular effective refractory period (VERP) and conduction were examined in an electrophysiologic study of 9 patients at drug-free baseline, after 14 days of dlsotalol administration (320mg/day), and after the administration of isoproterenol. In all 9 patients, ventricular tachyarrhythmia could not be induced after dl-sotalol treatment. Isoproterenol was administered as a loading dosage of 0.025μg/kg for 5min with a maintenance dosage of 0.0025μg/kg/min. The VERP and the QRS duration were determined at paced cycle lengths of 600, 400 and 300msec. DL-sotalol and dl-sotalol+isoproterenol had no effect on ventricular conduction at the three cycle lengths. The VERP was significantly prolonged after dl-sotalol treatment at paced cycle lengths of 600 (241±16 to 302±28msec, p<0.001), 400 (223±21 to 280±23msec, p<0.001) and 300msec (202±16 to 256±24msec, p<0.005), but there was a parallel shift of the VERP, suggesting the absence of use-dependent effects on the VERP. The dl-sotalol-induced VERP prolongation was partially reversed by isoproterenol, but it remained significantly prolonged above baseline values at paced cycle lengths of 600 (241±16 to 281±18msec, p<0.01), 400 (223±21 to 258±20msec, p<0.01) and 300msec (202±16 to 247±22msec, p<0.01). The shortening of the VERP was greater at longer basic cycle lengths (600 and 400msec) than at the shorter paced cycle length (300msec, p<.05), but the percentage increase of the VERP was similar at the three basic cycle lengths of 600 (16%), 400 (15%) and 300 (20%)msec, indicating the lack of reverse use-dependency. The absence of reverse use-dependency of dl-sotalol on the VERP, even after isoproterenol administration, may be beneficial in the therapy of ventricular tachyarrhythmias and may account in part for the high efficacy of this drug.