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This study investigated the effect of an intravenous serotonin reuptake inhibitor on the neural substrates of obsessive-compulsive disorder (OCD), as intravenous agents may be more effective in treating OCD than conventional oral pharmacotherapy. Eight OCD subjects and eight control subjects received alternate infusions of citalopram and placebo during functional magnetic resonance imaging, in a randomized, symptom-provocation, crossover design. Compared with baseline, OCD subjects displayed significant changes in prefrontal neural activity after the citalopram infusion relative to placebo, and these changes correlated with reductions in subjective anxiety.