OBJECTIVE: We examined the relationship between 5HTTLPR genotype and volume of magnetic resonance imaging (MRI) brain lesions. METHOD: We studied 217 older depressed patients and 141 individuals in the comparison group using a standard brain MRI protocol to calculate lesion volumes. Genotype at 5HTTLPR was determined for each subject. RESULTS: In age-adjusted models, the l/s genotype was associated with increased volume of total and white-matter lesions among depressed patients. This relationship lost significance in models controlling for reported hypertension. CONCLUSIONS: The finding that 5HTTLPR heterozygotes have higher vascular lesion volumes may be related to development of hypertension.