First-ever stroke patients (n=20) with a DSM-IV diagnosis of major depressive disorder (MDD) were included in an open-label study and received a single oral dose (50-100 mg) of the selective serotonin reuptake inhibitor sertraline. At days 0, 7, 14, 28, 42, and 56, a psychometric test battery comprising the Hamilton rating scales for depression and anxiety, the Mini Mental State Examination and the Barthel Index was administered. At the endpoint, 9 (45%) of the subjects were no longer depressed, 4 (20%) presented minor depression, and 7 (35%) still suffered from MDD. Considering the whole group of treated patients, depression and anxiety symptoms were found to decrease continuously and cognitive and functional performances to improve continuously during the treatment. Furthermore, differences between the values recorded by the treatment responders and non responders at the end of follow up were highly significant (p<0.02 for all comparisons). This report suggests that sertraline treatment of post-stroke MDD could be effective and well tolerated. However, non responders to the treatment are at risk of poor outcome. Double blind studies with a greater number of patients are necessary to confirm these preliminary results.