OBJECTIVE A role for endothelin-1, a potent vasoconstrictor peptide, in some cerebrovascular diseases has been proposed. To obtain preliminary data about peripheral concentrations of endothelin-1 in acute cluster headache, we measured the plasma endothelin-1 secretory pattern in 10 men with cluster during and independent of a headache attack. METHODS We collected blood samples for plasma endothelin-1 determinations at 0, 15, 30, 45, 60, 90, and 120 minutes during a cluster attack and closely monitored blood pressures. We repeated the same sampling during an asymptomatic period. RESULTS The mean values of plasma endothelin-1 (before a cluster headache, 3.3 +/- 0.3 pg/mL) significantly increased (F = 2.578, P < .05) during an attack, reaching their peak at 30 minutes (5.0 +/- 0.5 pg/mL, P < .05). We found no significant variations in mean arterial pressure. CONCLUSIONS Endothelin-1 may play a role in the pathophysiology of cluster attacks. The increase in plasma observed during cluster attacks may be linked to alterations in systemic hemodynamics and vascular tone.