In patients with cyanotic congenital heart disease (CCHD) a right to left shunt results in systemic hypoxemia. Systemic hypoxemia incites a compensatory erythrocytosis, which increases whole blood viscosity. We considered that these changes might adversely influence myocardial perfusion in CCHD patients. Basal and hyperemic (IV dipyridamole) perfusion measurements were obtained with N-13 ammonia positron emission tomographic (PET) imaging in left (LV) and right (RV) ventricular and septal myocardium in 14 adults with CCHD (age: 34.1±6.5 yrs; hematocrit: 62.2±4.8%) and 10 healthy controls (age: 37.8±4.8 yrs). In patients, basal perfusion measurements were higher in LV (0.77±0.24 versus 0.55±0.09 ml/min/g, p<0.05), septum (0.71±0.16 versus 0.49±0.09 ml/min/g, p<0.001) and RV (0.77±0.30 versus 0.38±0.09 ml/min/g, p<0.001). However, basal measurements normalized for the rate-pressure product (RPP) were similar to controls'. Calculated oxygen delivery relative to RPP was higher in the patients: 2.2±0.8 versus 1.6±0.4 x10^-5 ml O₂/ per min/g tissue/beats*mm Hg in the LV (p<0.05), and 2.0±0.7 versus 1.4±0.3 x10^-5 ml O₂/ per min/g tissue/beats*mm Hg in the septum (p<0.01). Hyperemic perfusion measurements in CCHD patients did not differ from controls (LV 1.67±0.60 versus 1.95±0.46 ml/min/g; septum 1.44±0.56 versus 1.98±0.69 ml/min/g; RV 1.56±0.56 versus 1.65±0.64 ml/min/g, p=NS), and coronary vascular resistances were comparable (LV 55±25 versus 48±16 Hg/ml/g/min; septum 67±35 versus 50±21 Hg/ml/g/min; RV 59±26 versus 61±27 mm Hg/ml/g/min, p=NS). These findings suggest that adult CCHD patients have remodeling of the coronary circulation to compensate for the rheologic changes attending chronic hypoxemia.