Subcutaneous treatment of chronic tension-type headache with 2 mg and 4 mg sumatriptan, a selective 5-hydroxytryptamine1-like receptor agonist, was compared with placebo in a double-blind crossover study of 36 patients. The effect was evaluated using a 6-point verbal relief rating scale and by visual analog scale ratings of headache intensity before and for 2 h after treatment. Sumatriptan induced a modest but significantly greater headache relief than placebo, whereas no significant difference was found between the two doses of sumatriptan. Headache relief following sumatriptan was significant after 60 min and still seemed to be increasing after 120 min when the examination terminated. Three possible mechanisms of action of sumatriptan in tension-type headache are discussed.