Ten patients with migraine with prolonged aura were studied for the presence of mitochondrial DNA point mutations utilizing DNA isolated from blood and hair samples. We analyzed for nine point mutations reported in patients with MELAS (A3243G, C3256T, T3271C, T3291C, A5814G, T8356C, T9957C, G13513A, and A13514G) and three secondary LHON mutations (T4216C, A4917G, and G13708A). None of the patients tested had any of these mutations in mitochondrial DNA. However, one patient was found to have a tRNA(Gln) A4336G mitochondrial DNA variant. From this study it appears that migraine with prolonged aura is not an oligosymptomatic form of MELAS and is not related to secondary LHON mutations. The significance of the tRNA A4336G variant is unknown.