Norepinephrine, an alpha 1,2-beta 1,2-adrenergic agonist, seems to be an alternative to epinephrine, an alpha 1,2-beta 1,2-agonist, for restoration of spontaneous circulation in VF. We therefore studied the effect of epinephrine and norepinephrine on MDO2 and MVO2 using OCCM after five minutes of cardiopulmonary arrest in 21 pigs. After OCCM of three minutes, seven animals each received placebo (controls) or epinephrine (45 micrograms/kg) or norepinephrine (45 micrograms/kg). All drugs were given blindly. At 90 seconds after epinephrine or norepinephrine, mean arterial blood pressure was significantly higher than in the control group. Prior to cardiac arrest, MBF, measured with radioactive microspheres, was 193 +/- 30 ml/min/100 g. During CPR but before drug administration, MBF was 51 +/- 23 in the control group, 71 +/- 10 in the group with epinephrine, and 74 +/- 11 ml/min/100 g in the group with norepinephrine. At 90 seconds after epinephrine, MBF increased to 126 +/- 18 and after norepinephrine to 107 +/- 30 ml/min/100 g (p less than 0.05). Compared to OCCM alone, MDO2 increased from 9.6 +/- 1.7 to 17.1 +/- 3.2 ml/min/100 g after epinephrine and from 9.4 +/- 1.8 to 13.6 +/- 4.2 ml/min/100 g after norepinephrine (p less than 0.05). There was an increase in MVO2 from 4.0 +/- 1.5 to 9.4 +/- 3.0 ml/min/100 g after epinephrine (p less than 0.05), whereas MVO2 increased only from 4.2 +/- 0.8 to 5.1 +/- 2.0 ml/min/100 g after norepinephrine. Because epinephrine led to a greater increase in MVO2 than norepinephrine, the myocardial oxygen ER remained unchanged. The oxygen requirements of the fibrillating heart seemed to be increased via beta 2-adrenergic stimulation. In both the control and epinephrine-treated groups, only three of the seven animals could be successfully resuscitated, whereas all of the animals in the group with norepinephrine survived the 15-minute period of observation. In this model, norepinephrine, in contrast to epinephrine, improves the balance between MDO2 and MVO2 and eases restoration of spontaneous circulation.