Although increases in serum epinephrine are known to cause hypokalemia, the epinephrine dosages and concentrations at which this effect occurs, and the electrocardiographic consequences, have not been evaluated. Because epinephrine infusion is now being used to provoke arrhythmias in some patients, we have determined the physiologic effects of a range of dosages of epinephrine. The effects of pretreatment with propranolol and diltiazem on these indexes of epinephrine effect were also evaluated. Epinephrine dose ranging started at 10 ng/kg/min, with doubling of the dose every 10 minutes until a predetermined end point was reached. At the end of each dosage level, serum electrolytes, catecholamines, and an electrocardiogram were recorded. Whereas even the lowest dosage of epinephrine significantly increased heart rate, serum glucose levels increased and serum potassium decreased only when dosages of 160 to 320 ng/kg/min were administered. Plasma concentrations of epinephrine at these dosages were mean +/- SD 1,328 +/- 902 pg/ml, comparable to those observed in these subjects during maximal exercise (1,003 +/- 527 pg/ml). The major electrocardiographic effect of epinephrine infusion was a dose-related increase in QTc, but pretreatment with propranolol blunted this effect and tended to shorten QTc. At an epinephrine dose of 40 ng/kg/min, QTc prolongation persisted and was inhibited by diltiazem. These data suggest that the major electrocardiographic effect of epinephrine infusion is mediated by increased calcium current. At dosages > 80 ng/kg/min, plasma epinephrine concentrations are comparable to those observed with severe stress, and hypokalemia is common. The use of epinephrine as an electrophysiologic provoker at dosages > 80 ng/kg/min results in both a direct effect, as well as an indirect effect due to hypokalemia.