This study was made in an attempt to document the effects of early treatment of poststroke depression (including fluoxetine treatment) on neuropsychological rehabilitation (including cognitive function). Assessment measures used included the Schedule for Affective Disorders and Schizophrenia (SADS) and Research Diagnostic Criteria (RDC), as well as standard measures of severity of depression, functional ability, cognitive function, and neurological function. Thirty-seven patients with poststroke depression, treated with fluoxetine (n = 26) or nortriptyline (n = 11), were compared with 11 poststroke depressed patients who received no depression treatment and 82 poststroke nondepressed patients who received no depression treatment. Our findings about the prevalence of depression (37%), more frequent with anterior lesion (p = .009) and left hemisphere lesion (not statistically significant), tend to confirm previous reports. Early treatment (4th week poststroke) with either fluoxetine or nortriptyline significantly improved the depressed patients' mood, neurological function, functional ability, and cognitive ability. A close relationship between appropriate early treatment (including fluoxetine treatment) of poststroke depression and improved neuropsychological rehabilitation (including cognitive improvement) is suggested by our findings. This is the first report, to our knowledge, of the beneficial effects of early antidepressant treatment on the cognitive function of poststroke depressed patients.