A pericardial effusion is easily recognized by echocardiography, but the diagnosis of cardiac tamponade by echocardiography is controversial. Recently, several reports have indicated that right ventricular (RV) or right atrial (RA) diastolic collapse represent highly specific and sensitive signs of a hemodynamically significant pericardial effusion. This report evaluates the pathophysiologic significance of these findings in 3 patients. One patient had classic clinical and hemodynamic features of tamponade without typical echocardiographic features; 1 had typical echocardiographic features of tamponade without the characteristic clinical or hemodynamic features; and 1 had all the findings characteristic of tamponade, including mechanical and electrical alternans. The first patient had increased right-sided cardiac pressures and RV hypertrophy, which prevented RV or RA collapse. The second patient had low right-sided intracardiac pressures, which allowed RV and RA diastolic compression to occur during early and mid-diastole. In the third patient, severe holodiastolic impairment of right-sided filling, and presumed decreased pulmonary venous and pericardial compliance, in the setting of tamponade produced a beat-to-beat alternation of RV and left ventricular filling with associated electrical and mechanical alternans. RV or RA collapse during diastole occurs when intrapericardial pressure equals or exceeds intracardiac pressure. Increases in wall stiffness of chamber pressures may prevent diastolic collapse in the setting of tamponade. Conversely, extremely low intracardiac pressures may allow diastolic collapse to occur in the absence of overt cardiac tamponade. The extent and timing of the RA or RV collapse, rather than its mere occurrence, are important in the diagnosis of cardiac tamponade by echocardiography.