Experimental studies and investigations of the cerebrospinal fluid in migraineurs have suggested an involvement of brain-derived neurotrophic factor (BDNF) in migraine pathophysiology. In a case-control study approach, the functional Val66MET polymorphism (rs6265) of the BDNF gene was investigated in 265 migraine patients and 153 controls. Genotype and allele frequencies did not differ between healthy subjects and migraineurs. A subgroup analysis for the occurrence of aura or clinical characteristics, including the number of attacks, did not reveal a positive association for the investigated polymorphism. Our data argue against a role of this well characterized BDNF gene variant as a risk factor in migraine.