We conducted the present study to determine if pharmacologically recruitable flow reserve was present during ischemia in unanesthetized dogs studied in the absence of adrenergic activation. Microsphere measurements of regional perfusion at reduced coronary pressures in a distal circumflex region subjected to intracoronary adenosine infusion (0.265 mg/min IC) were compared with measurements in a proximal circumflex region where pressure was reduced but flow was being autoregulated normally. Ischemia began when coronary pressure was reduced below 40 mm Hg. At a coronary pressure of 28 +/- 1 (mean +/- SEM) mm Hg, subendocardial flow with autoregulation intact was 0.59 +/- 0.05 mL.min.g-1 and similar to that in the region receiving adenosine, which averaged 0.61 +/- 0.05 mL.min-1.g-1 (P = NS). Although adenosine increased subepicardial flow from 0.81 +/- 0.05 to 1.16 +/- 0.09 mL.min-1.g-1 (P < .001), the magnitude of the increase was minimal when coronary pressure fell to a level that caused subepicardial flow during autoregulation to be reduced below resting values. These results demonstrate that the substantially lower autoregulatory break point found in unanesthetized dogs studied in the basal state reflects the ability of intrinsic autoregulatory mechanisms to match local vasodilator reserve to that recruitable pharmacologically. This contrasts with the presence of pharmacologically recruitable subendocardial flow reserve in anesthetized animals and is most likely related to a low level of circulating catecholamines and lack of sympathetic activation in unanesthetized animals studied under basal conditions.