We studied the effect of standard and high doses of epinephrine on coronary perfusion pressure during cardiopulmonary resuscitation in 32 patients whose cardiac arrest was refractory to advanced cardiac life support. Simultaneous aortic and right atrial pressures were measured and plasma epinephrine levels were sampled. Patients remaining in cardiac arrest after multiple 1-mg doses of epinephrine received a high dose of 0.2 mg/kg. The increase in the coronary perfusion pressures was 3.7 ± 5.0 mm Hg following a standard dose, not a statistically significant change. The increase after a high dose was 11.3 ± 10.0 mm Hg; this was both statistically different than before administration and larger than after a standard dose. High-dose epinephrine was more likely to raise the coronary perfusion pressure above the previously demonstrated critical value of 15 mm Hg. The highest arterial plasma epinephrine level after a standard dose was 152 ± 162 ng/mL, and after a high dose, 393 ± 289 ng/mL. Because coronary perfusion pressure is a good predictor of outcome in cardiac arrest, the increase after high-dose epinephrine may improve rates of return of spontaneous circulation.