Computer models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. We have used novel techniques to build a structurally-detailed, image-based model of 3-D atrial anatomy. A volume image of the atria from a normal sheep heart was acquired using serial surface macroscopy, then smoothed and down-sampled to 50 μm(3) resolution. Atrial surface geometry was identified and myofiber orientations were estimated throughout by eigen-analysis of the 3-D image structure tensor. Sinus node, crista terminalis, pectinate muscle, Bachman's bundle, and pulmonary veins were segmented on the basis of anatomic characteristics. Heterogeneous electrical properties were assigned to this structure and electrical activation was simulated on it at 100 μm(3) resolution, using both biophysically-detailed and reduced-order cell activation models with spatially-varying membrane kinetics. We confirmed that the model reproduced key features of the normal spread of atrial activation. Furthermore, we demonstrate that vulnerability to rhythm disturbance caused by structural heterogeneity in the posterior left atrium is exacerbated by spatial variation of repolarization kinetics across this region. These results provide insight into mechanisms that may sustain paroxysmal atrial fibrillation. We conclude that image-based computer models that incorporate realistic descriptions of atrial myofiber architecture and electrophysiologic properties have the potential to analyse and identify complex substrates for atrial fibrillation.