Adenosine is a powerful natural vasodilator that could be involved in migraine. It is difficult to assay this nucleoside, however, because it has a short half-life. We have used HPLC to compare the concentrations of blood adenosine sampled in crisis-free intervals and during crisis periods in ten patients with common migraine and have compared these levels to those noted in a control population. Our sampling technique uses vacuum suction and enables rapid mixing of the blocking solution and whole venous blood. This results in reproducible HPLC assays. We also show that, during a migraine crisis, mean blood adenosine levels increase by 47%. However, the origin of this adenosine release is difficult to define.