From the earliest pathological studies the perivenular localization of the demyelination in multiple sclerosis (MS) has been observed. It has recently been suggested that obstructions to venous flow or inadequate venous valves in the great veins in the neck, thorax and abdomen can cause damaging backflow into the cerebral and spinal cord circulations. Paolo Zamboni and colleagues have demonstrated abnormal venous circulation in some multiple sclerosis patients using non-invasive sonography and invasive venography. Furthermore, they have obtained apparent clinical improvement or stabilization by endovascular ballooning of points of obstruction in the great veins in some, at least temporarily. If non-invasive observations by others validate their initial observations of a significantly increased prevalence of venous obstructions in MS then trials of angioplasty/stenting would be justified in selected cases in view of the biological plausibility of the concept.