Previous studies have suggested that the endogeneous psychotomimetic molecule bufotenine (N-N notdimethyl-5-idroxytryptamine) may play a role in the pathogenesis of severe mental disorders. The potential association of bufotenine with the clinical features of autism and schizophrenia is not entirely understood. In this study, we measured urinary levels of bufotenine in subjects with autistic spectrum disorder (ASD), schizophrenia and healthy comparison subjects free of psychiatric symptoms. We also sought to assess whether urine concentrations of this molecule may be associated with the clinical characteristics of psychiatric patients. DESIGN: Urine bufotenine levels were measured using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay in young adults with severe ASD (n = 15), patients with schizophrenia (n = 15), and healthy control subjects (n = 18). The Vineland Adaptive Behavior Scale was used to measure adaptive behaviors in ASD individuals. The Brief Psychiatric Rating Scale (BPRS) was used for patients with schizophrenia. RESULTS: Urine bufotenine levels were significantly higher in ASD subjects (3.30 +/- 0.49 mug/L, P < 0.05) and patients with schizophrenia (4.39 +/- 0.43 mug/L, P < 0.001) compared with controls (1.53 +/- 0.30 mug/L). Among patients with ASD, there was a significant positive correlation between urine bufotenine and hyperactivity scores on the Vineland Adaptive Behavior Scale (r = 0.479, P < 0.05). No other associations were detected. CONCLUSIONS: our results indicate that elevated urine levels of the endogeneous psychotomimetic molecule bufotenine may play a role in ASD and schizophrenia, and can be correlated with hyperactivity scores in autism