Abnormal coronary blood flow (CBF) in long-standing left ventricular (LV) pressure-overload hypertrophy has been associated with ischemia and LV dysfunction. Thus, goals of therapy in pressure overload are not only the relief of the overload itself but also regression in hypertrophy and subsequent improvement in CBF. However, little is known about CBF in humans or in large mammals after the relief of pressure overload, when the hypertrophy has regressed. This study was performed to test the hypothesis that, even 6 months after the relief of pressure overload in the dog, CBF would still be abnormal. Three groups of dogs were studied: 1) normal control dogs (NL group), 2) dogs with LV pressure-overload hypertrophy (LVH group), and 3) dogs that had developed LV pressure-overload hypertrophy but in whom the pressure overload was relieved 6 months before the final study (LVH Reg group). CBF was studied in conscious dogs by use of the radiolabeled microsphere technique at rest, during rapid atrial pacing, and during maximum coronary vasodilation produced by adenosine infusion. The ratio of LV weight (g) to body weight (kg) (LVBW) was 4.2±03 in the NL group, 7.1±0.6 in the LVH group, and 7.7±0.5 in the LVH Reg group before pressure-overload relief (p=NS, LVH versus LVH Reg). Six months after removal of the pressure overload, the LVBW in the LVH Reg group had fallen to 5.5±0.3 (p<0.05), but this LVBW was still greater than that in the NL group (p<0.05). During rapid atrial pacing, endocardial and epicardial CBF rose significantly in NL dogs. However, during rapid atrial pacing, endocardial CBF fell from 1.18±0.22 to 0.7±0.20 ml/min per gram in the LVH group (p<0.05) and did not rise in the LVH Reg group. During adenosine infusion, endocardial blood flow increased in NL dogs from 1.63±0.13 to 4.0±0.3 ml/min per gram and increased to a similar level in the LVH Reg group. Although CBF increased during adenosine infusion in the LVH group, the increase was less than that in the NL or LVH Reg group (p<0.05). Minimum coronary vascular resistance was similar in NL dogs (14±2 units) and LVH Reg dogs (18±3 units,p=NS) but was significantly elevated (32±10 units) in LVH dogs (p<0.05). We conclude that after significant but incomplete regression of pressure-overload hypertrophy, maximum CBF and minimum coronary vascular resistance return to normal. However, during rapid atrial pacing, significant abnormalities in CBF still exist.