Forty out-patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society (IHS) Headache Classification Committee. In a controlled trial patients received placebo for a four-week baseline period, then they were randomized in double-blind fashion to therapy with mianserine (30-60 mg/day) of fluvoxamine (50-100 mg/day) for another eight-week period. Frequency of headache, pain severity and analgesic consumption were evaluated using a self-monitoring system. Mood depression was evaluated at 0, 4 and 8 weeks by using Zung's Self-Rating Depression Scale and Hamilton Rating Scale for Depression. Both drugs were beneficial in the treatment of chronic tension-type headache. Non-depressed subjects with more severe headache responded best to fluvoxamine, whereas mianserine was more effective in the treatment of depressed patients with moderate headache. These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients.