Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.