Tension headache (TH) is one of the most frequent types of idiopathic headaches. The leading role in its pathogenesis is played by depression and dysmetabolism of the neurotransmitter serotonin. The subjects were 100 patients with TH. The examination included study of headache intensity, complex psychometric testing, and immune-enzyme measurement of serotonin serum level, performed before and after treatment with the anti-depressant prodep. All the patients had moderate pain syndrome, depression, and moderate or severe anxiety, which demonstrated negative correlation with serotonin serum level. In particular, the intensity of episodic THs (n = 24) was 52 mm visual analogue scale, reactive anxiety level was as high as 51.08 +/- 4.2, the level of depression was moderate (12.9 Beck scale); serotonin blood level showed a tendency to fall (205.72 +/- 6.74 ng/ml). In 76 patients, suffering from chronic THs with a cephalgia intensity of 62 mm visual analogue scale, high indexes of reactive and personal anxiety (46.81 -/+ 2.68 and 54.2 +/- 3.64, respectively), and high depression level were associated with a prominent decrease of serotonin blood concentration (119.38 +/- 9.42 ng/ml). A course of treatment with prodep led to significant decrease of headache intensity and improved depression, while an increase of serum serotonin level was observed. Thus, serotonin serum level may be used as a marker of pain intensity and the level of depression, and an objective indicator of anti-depressive therapy.