In a subset of patients, atrial fibrillation is caused by rapidly firing foci that are often located in the pulmonary veins especially when fibrillation is paroxysmal. Histologic data show that myocardial tissue of the left atrial wall extends into the pulmonary venous walls. Both in dog and human pulmonary veins, arrangement of the myofibers is complex. Clinical and animal studies reveal both double potentials and fractionated electrograms in the pulmonary veins, which are related to the complex architecture of the myocardial sleeves in the veins. Such a structure supports the occurrence of reentry. As well, the reduced coupling of cells at sites with abrupt changes in fiber direction could facilitate the escape of a focus and subsequent activation of surrounding tissue. Intracellular recordings made in the pulmonary veins of guinea pig and dog hearts showed that spontaneous activity can occur. Spontaneous action potentials with phase 4 depolarization as well as early after depolarizations were observed in these animal models. In non-spontaneously active preparations, spontaneous activity could be provoked by pharmacologic interventions. The cycle length of bursts of ectopic beats arising in the pulmonary veins of man is often irregular, supporting a focal mechanism of the ectopic beats. The anisotropic characteristics of the myocardial sleeves in the veins may increase the ability of a focus to become evident.