RATIONALE: We have previously demonstrated that antidepressant medication facilitates the processing of positive affective stimuli in healthy volunteers. These early effects of antidepressants may be an important component in the therapeutic effects of antidepressant treatment in patients with depression and anxiety. OBJECTIVES: Here we used functional magnetic resonance imaging in a double-blind, randomised, placebo-controlled between-groups design to investigate the effects of short-term (7-10 days) treatment with the selective serotonin reuptake inhibitor, citalopram, on the amygdala response to positive and negative facial expressions in healthy volunteers. RESULTS: Citalopram was associated with increased amygdala activation to happy faces relative to placebo control, without changes in levels of mood or anxiety. CONCLUSIONS: These early, direct effects of antidepressant administration on emotional processing are consistent with a cognitive neuropsychological model of antidepressant action.