When performing coronary angioplasty, guide catheter intubation of the ostium often leads to a damping of the pressure tracing. In contrast, when a guide catheter with side holes is used, the pressure tracing is most often superimposable to the pressure wave recorded through the side arm of a femoral artery sheath introducer. This pressure wave gives the reassuring impression of normal hemodynamics in the coronary artery. To illustrate the role of guide catheter side holes and that guide catheter pressure does not necessarily equal the actual coronary artery perfusion pressure, we report observations on trans-ostial pressure gradients at rest and during increased coronary flow rates. An abbreviated in vivo study of side holes on the maximal achievable blood flow, employing timed blood flow collections in 7F and 8F side hole guide catheters, was made in 10 patients. At high mean aortic pressure levels, the blood flow through the side holes did not exceed 80 and 60 mL/min for 8 and 7F guide catheters, respectively. These observations suggest that, under some conditions, the guide catheter may produce a resting or hyperemic trans-ostial gradient and that the flow provided only by the side holes of guide catheter is limited. Guide catheter interference with normal flow should be considered in interventional procedures even when arterial pressure appears normal.