Brain magnetic resonance imaging (MRI) allows for quantitative assessment of hyperintense foci, which are seen with aging and various diseases. These foci, considered to represent lesions, are important in the study of various psychiatric illnesses, including depression. Few quantitative measures have been developed for such research. The goal of the current study was to develop a reliable and efficient method for quantifying the volumes of gray and white matter lesions in MRI scans of the elderly. Interrater reliability was determined by repeat lesion measures on 16 scans. Semi-automated segmentation was performed that identified potential lesions, and then lesions were manually selected based upon detailed anatomic criteria. The lesion quantification procedure took between 25 and 45 min per scan. Reliability intraclass correlation coefficients (ICCs) were 0.99 for both gray and white matter lesions. Volumetric results were found to be moderately correlated with previous lesion ratings (r-values between 0.37 and 0.62, P<0.0001). Among the 700 scans processed with this method, lesion volumes ranged from 0 to 7.3 ml for gray matter, and from 0.4 to 96.8 ml for white matter. Our method proved to be efficient and reliable for quantifying lesions in MRI scans of the elderly.