Clinical and pharmacological data suggest a derangement of central monoaminergic systems in tension-type headache. Biochemical evidence has been rarely recognized. These findings may relate with pathophysiological mechanisms of headache or with underlying depression. We measured platelet-rich plasma serotonin and plasma catecholamines (norepinephrine, epinephrine, and dopamine) in 30 patients with tension-type headache and in 20 healthy controls, using High-Pressure Liquid Chromatography. We studied differences between groups and the relation between biochemical parameters and clinical indices evaluating duration and severity of headache and depression. Platelet serotonin levels in tension headache patients were higher than in controls (P < 0.001). Plasma catecholamine levels were lower in patients than in controls (P < 0.001 for epinephrine and dopamine, and P < 0.05 for norepinephrine). There was a positive correlation between dopamine levels and duration of history of headache (r = 0.55, P < 0.05). A negative correlation between epinephrine levels and severity of headache was observed (r = 51, P < 0.01). No correlations were found between monoamine levels and severity of depression. Our results add to the evidence of alterations of monoaminergic central systems in tension-type headache patients. These alterations seem to be independent from the underlying depression and related to the pathophysiologic mechanisms of headache.