Serotonin (5HT) binds in a saturable and specific manner to high affinity binding sites present on the surfaces of human lymphocytes and monocytes. We reported that migraine patients have an increase in 5HT binding parallel to the progression of the attack, with the appearance of a subsequent phenomenon of cellular deactivation. The same experiment previously carried out in cluster headache patients revealed a lack of high affinity binding sites, independently of the pain period. Low levels of plasma 5HT were recently described by Anthony in chronic tension-type headache. The implication of 5HT in tension headache was also hypothesized by Shukla with the demonstration of an increased 5HT uptake by platelets. We studied the 5HT binding on surfaces of lymphocytes and monocytes in 26 tension-type headache patients (16 affected by chronic form (CTH) of the disease and 10 by episodic form (ETH]. Fourteen clinically healthy subjects were used as controls. Circulating lymphocytes and monocytes were tested for their ability to specifically bind 5HT, using (3H) labeled 5HT. The "in vitro" 5HT binding curves to lymphocytes and monocytes of tension-type headache patients show a constant trend; during headaches, both CTH and ETH patients present a desensitization phenomenon with a complete loss of high affinity binding sites for 5HT. The 5HT binding curve observed in controls is indistinguishable from that of ETH patients studied outside the attack period. The total amount of 5HT bound appeared to be more markedly raised in CTH patients than in ETH patients when compared to control values.(ABSTRACT TRUNCATED AT 250 WORDS)