OBJECTIVES: Post-stroke depression and pathological crying (PC) implicate an imbalance of serotonergic neurotransmission. We claim that PC follows serotonin depletion that raises the binding potential (p(B)) of the 5-HT(1A) receptor antagonist [carbonyl-(11)C]WAY-100635, which is reversible by selective serotonin re-uptake inhibitor (SSRI) treatment. MATERIALS AND METHODS: We PET scanned patients with acute stroke and PC and age-matched control subjects. Maps of receptor availability were generated from the images of eight cortical regions and raphe nuclei. RESULTS: The maps showed highest binding in limbic areas and raphe nuclei, while binding in basal ganglia and cerebellum was negligible. Baseline binding potentials of patients were lower than that of control subjects (3.7 +/- 0.6 vs 4.2 +/- 0.2). Treatment with SSRI markedly reduced free receptor sites, whereas placebo administration led to a global increase. DISCUSSION: The study is the first suggestion of changes of serotonergic neurotransmission in the early phase of stroke and the modulation of these changes with SSRI treatment.