Concentrations of 5-hydroxytryptamine (5-HT) in platelets were determined in 33 cluster headache patients (17 males) and in 34 migraine patients (16 males) outside attacks. The 5-HT uptake into platelets was measured and the kinetic constants Vmaxand Kmdetermined in 26 cluster patients (14 males) and in 30 migraine patients (13 males). Significantly lower 5-HT concentrations in whole blood were found in cluster headache and migraine patients than in 50 healthy controls (19 males). The Vmaxand Kmvalues of the 5-HT uptake were significantly lower in cluster headache and migraine patients compared with 22 healthy controls (9 males). The 5-HT concentrations and the kinetics of the 5-HT uptake did not differ between cluster headache and migraine. In healthy controls a significant positive correlation was found between the 5-HT uptake rate at 0.25 μM and Kmbut not in cluster headache and migraine patients. The 5-HT concentrations in whole blood correlated positively with Vmaxand Km, respectively, in cluster headache and with Kmin healthy controls but not with Vmaxnor with Kmin migraine. There was no obvious relation between the kinetics of platelet monoamine oxidase (MAO) and the 5-HT uptake except for an increased incidence of low Vmaxof MAO and low Kmof the 5-HT uptake in cluster headache. The kinetics of the 5-HT uptake was apparently not related to the state of migraine. The results indicate a possible constitutional trait in cluster headache and migraine expressed as low 5-HT concentrations in whole blood and low Vmaxand Kmof the 5-HT uptake into platelets.