Histamine, 0.16, 0.33 and 0.66 microgram/kg/min, was infused intravenously to 13 normal non-headache-prone volunteers, 10 patients with chronic muscle contraction headache and 25 patients with common migraine. In the normal group no patients developed pulsating headache. In the migraine group 13 patients developed severe, 9 patients moderate and 2 patients mild pulsating headache, and only 1 patient failed to develop headache at all. The muscle contraction headache patients responded intermediately. At each infusion rate the headache was of constant quality and severity as long as the infusion continued, but disappeared shortly after its termination. Injection of an H1 blocking agent, mepyramine, almost immediately abolished the headache. The H2 blocker cimetidine was much less effective, but still significantly better than placebo. The i.v. histamine infusion test is a useful model for the study of experimental vascular headache.