The effect of i.v. dobutamine on acute myocardial ischemic injury was assessed in 22 anesthetized dogs subjected to serial 10-minute occlusions of the left anterior descending coronary artery. The severity of ischemic injury was determined by mass spectrometric measurement of the increase in intramural carbon dioxide tension (delta PmCO2) in the ischemic zone. In the time protocol 1 dogs, dobutamine, 20 micrograms/kg/min, infused between the control and final occlusion, significantly increased both heart rate (HR) and left ventricular (LV) dP/dt; delta PmCO2 was significantly higher during the dobutamine infusion that during control occlusion (76 +/- 21 vs 56 +/- 13 mm Hg, p less than 0.01). The nine protocol 2 dogs were atrially paced at a HR of 20--30 beats/min above baseline values during the control occlusion and received dobutamine (12.6 +/- 7.8 micrograms/kg/min) at doses necessary to attain an equal HR (mean 149--154 beats/min) during the last occlusion. Although LV dP/dt was higher after dobutamine, delta PmCO2 was similar during the two occlusions. Protocol 3 dogs (n = 4) received lower doses of dobutamine (5.6 +/- 3.2 micrograms/kg/min) to produce an increase in LV dP/dt, but not in HR compared with baseline values; delta PmCO2 was similar during control and dobutamine occlusions. There were no major change in arterial or left atrial pressures. Rate-pressure product, an indirect measurement of myocardial oxygen consumption, was increased only by the higher doses of dobutamine in protocol 1. Thus, inotropic stimulation with dobutamine during coronary occlusion does not cause important augmentation of acute myocardial ischemic injury in the nonfailing heart unless HR is increased simultaneously.