The event-related potential P300 has been studied in 15 migraine without aura sufferers, and in 15 episodic tension-type headache sufferers, during pain-free periods and during spontaneous headache attacks. There were no variations of potential, either of P3 latency or N2-P3 amplitude, in either group during the interictal period. Similarly, there were no variations of the P300 parameters in the group of tension-type headache subjects during headache attacks; by contrast, a significant elongation of latency (P < 0.01) and an increment of N2-P3 wave amplitude (P < 0.002) was observed in the group of migraineurs. The authors discuss the data in accordance with the etiopathogenic theories of migraine and the hypothesis that acetylcholine and norepinephrine are the neurotransmitter able to affect the event-related potential P300, which reflects cerebral activity during sensory information processing and analysis.