Background-Atrial fibrillation (AF) commonly associates with atrial dilatation by poorly understood mechanisms. We hypothesized that elevation of intra-atrial pressure elicits high-frequency and spatio-temporally organized left atrial ( LA) sources emanating from the superior pulmonary veins. Methods and Results-We used a stretch-related AF model in the sheep heart to induce stable episodes of AF (>40 minutes) in 9 animals. Video movies of the LA free wall ( LAFW) and LA superior pulmonary vein junction (JPV) were obtained by using di-4-ANEPPS. Electrograms from the right atrium were recorded. At intra-atrial pressures >10 cm H2O, the maximum dominant frequency (DFMax) was significantly higher in the JPV than in the LAFW (12.0 +/- 0.2 and 10.5 +/- 0.2 Hz, respectively [ mean +/- SEM]; P < 0.001). Below 10 cm H2O, DFMax was similar in the JPV and LAFW (10.8 ± 0.3 versus 10.2 ± 0.3 Hz; P = 0.6); DFMax in both JPV and LAFW was significantly higher than in the right atrium (7.8 ± 0.3 Hz; P < 0.001). Analysis of excitation direction in JPV showed positive correlation between intra-atrial pressure and the number of waves emanating from the left superior pulmonary vein (r = 0.79, P = 0.02) but not from the LAFW (r = 0.54, P = 0.09). The number of spatio-temporally periodic waves in the JPV correlated with pressure (r = 0.92, P = 0.002). In 3 cases, JPV rotors were identified with a cycle length equal to 1/DFMax. Conclusion-We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.