1. Our group has developed finite element models of ventricular anatomy that incorporate detailed structural information. These have been used to study normal electrical activation and re-entrant arrhythmia. 2. A model based on the actual three-dimensional microstructure of a transmural left ventricular (LV) segment predicts that cleavage planes between muscle layers may give rise to non-uniform, anisotropic electrical propagation and also provide a substrate for bulk resetting of the myocardium during defibrillation. 3. The model predictions are consistent with the results of preliminary experiments in which a novel fibre-optic probe is used to record transmembrane potentials at multiple intramural sites in the intact heart. Extracellular potentials are recorded at adjacent LV sites in these studies. 4. We conclude that structural discontinuities in ventricular myocardium may play a role in the initiation of re-entrant arrhythmia and discuss future studies that address this hypothesis.