Serum levels of tumor necrosis factor (TNF)-alpha/cachectin have been evaluated in 20 patients with Migraine without Aura (MwA) versus 17 patients with Chronic Type Tension Headache (CTTH). Results show an exaggerated release of TNF-alpha/cachectin in sera of patients affected by MwA, while in CTTH patients TNF serum concentration is comparable to that observed in normal donors. Some hypotheses are formulated in order to clarify the TNF-alpha/cachectin spontaneous production and its biological significance in patients with MwA.