Epigenetic silencing of a gene vital for motor neuron function could underlie sporadic ALS. We therefore examined the methylation status of two genes, SOD1 and VEGF, which are implicated in ALS. Methylation in the promoters of these genes was determined in white cell DNA (10 ALS patients) and brain DNA (six ALS patients). The promoter regions were largely unmethylated in all patients. Transcriptional silencing of these genes is therefore unlikely to be a common mechanism in ALS. However, in view of the potential for treatment of epigenetic disorders, promoter methylation in other genes required for motor neuron survival needs to be studied.