One hundred forty-eight patients, ages 18-65, with major depression were administered the Mini-Mental State Examination (MMSE) prior to 8 weeks of treatment with fluoxetine; 75 of these patients were readministered the MMSE following treatment. MMSE scores were not related to pretreatment severity of depression or to reported concentration problems and were not predictive of antidepressant response. Non- and partial responders had lower posttreatment MMSE scores than responders, men had lower posttreatment scores than women, and subjects over 50 had lower pretreatment scores than younger subjects, although in all cases, the magnitude of the differences was small and unlikely to be clinically important. Our results suggest that while the MMSE has been shown to be useful among geriatric and other depressed inpatients, it is not a sensitive indicator of depression severity, concentration problems, or likelihood of treatment response among otherwise healthy adults with major depression in an outpatient setting.