Depression is a common but often unrecognized complication after cerebrovascular stroke. Tricyclic antidepressants (TCA) have been found to be effective in poststroke depression, but side effects such as orthostatic hypotension, arrhythmia limit their wider use. In this pilot study the effects of treatment with the specific serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg) in 10 severely depressed patients (HAM-D score between 27 and 35) after cerebrovascular stroke were investigated. Four patients dropped out of the study prematurely because of worsening of their condition (n = 4) and one patient discontinued the study because of transfer to a nursing home. After 3 weeks of fluoxetine treatment there was a significant amelioration in all the measured scores (HAM-D, Beck, CGI and Barthel: P < 0.05). At the end of the study one patient with recurrent cerebrovascular lesions still had an HAM-D score of 25, but the other four patients had HAM-D scores between 6 and 11. The physical rehabilitation scores measured with the Barthel Index showed negative correlations with the HAM-D, Beck and CGI scores for most items; this has to be interpreted with caution considering the number of patients involved in this investigation. The authors suggest that future double blind trials are warranted to test the efficacy of fluoxetin therapy for poststroke depression. Methodological problems in connection with pharmacological trials in these severely ill patients are discussed.