Simultaneous plasma free and total tryptophan and CSF 5-HIAA concentrations were determined in 18 migraine patients during headache-free intervals, four hours and 24 hours after onset of headache. A statistically significant (p<0.05) positive correlation was found between CSF 5-HIAA and plasma free tryptophan 4 hours after onset of headache. No other statistically significant correlations were noted. Increased catecholamines resulting from stress (of migraine attack) can cause elevation of unesterified fatty acids which displace tryptophan from its binding to plasma albumin, making free tryptophan available to the brain for serotonin metabolism. The increased CSF 5-HIAA during the attack of migraine is related to stress, rather than to pathogenetic factors in the disorder.