Past research suggests a relationship between stress and positive symptoms of psychosis. However, the biological substrate of this relationship remains unknown. According to the transmethylation hypothesis, schizo- phrenia could result from a biochemical disruption in the stress mechanism. This biochemical disruption would lead to the production of a substance that would account for the symptoms of psychosis. Moreover, some studies have tes- ted endogenous N,N-dimethyltryptamine (DMT) in the context of the transmethylation hypothesis. Stress has been found to elevate DMT levels in rodents. Also, elevated DMT levels have been associated with positive features of psychosis in psychiatric patients. Additionally, healthy participants treated with exogenous DMT experience pre- dominantly positive symptoms of psychosis. The present paper examines endogenous DMT as a possible biological mediator of the relationship between stress and positive symptoms of psychosis. Keywords Dimethyltryptamine Transmethylation hypothesis Stress Positive symptoms of psychosis Schizophrenia Biological markers