BACKGROUND The classic increase in P wave size, known as 'P-atriale', is a widely accepted criterion for determination of proper positioning of central venous catheter tips. Recent transoesophageal echocardiography (TOE) studies did not confirm intra-atrial position despite advancing the central venous catheter further than indicated by ECG guidance. We postulate that the pericardial reflection rather than the entry into the right atrium corresponds to the ECG changes. In order to test our hypothesis we sought to determine the anatomical substrate for the electrical changes in an animal study. Subsequently, a modified version of the study was undertaken in man and is also reported. METHODS In six juvenile pigs the left external jugular vein and right carotid artery were cannulated. A triple-lumen central venous catheter was positioned by ECG guidance using a Seldinger wire as an exploring electrode. The venous and arterial catheters were suture fixed 2 cm beyond the onset of an increase in P wave size. The corresponding anatomical catheter tip position was determined by open exploration of the vessels and the heart. Subsequently the catheter tip position (during advancement) of a pulmonary artery catheter and the corresponding electrical ECG changes were examined in 10 patients during open chest cardiac surgery. RESULTS All catheters-arterial and venous, in animals and humans-revealed an increase in size of the P wave as well as the QRS complex. All venous catheters were positioned in the superior vena cava, beyond the pericardial reflection but outside the right atrium. All arterial catheters were positioned in the ascending aorta thus also beyond the pericardial reflection. CONCLUSIONS The start of an increase in P wave size does not correspond with the entrance of the right atrium. The anatomic equivalent for the electrophysiological changes of the ECG is the pericardial reflection. ECG guidance is unable to distinguish between venous and arterial catheter position.