The authors examined differences in antidepressant treatment response in geriatric outpatients with high vs. low levels of magnetic resonance imaging (MRI)-defined subcortical hyperintensities (SH). Participants included 59 outpatients with mild-to-moderate depression (mean age: 69+/-5.63 years; mean Hamilton Rating Scale for Depression score: 21+/-2.88) who participated in a placebo-controlled trial of sertraline and underwent a standardized brain MRI. Results revealed that the high-SH group was significantly older than the low-SH group but, contrary to the hypothesis, antidepressant treatment response did not differ between the high- and low-SH groups. The association between SH and antidepressant treatment response in depressed geriatric outpatients remains unclear and deserves further investigation.