This study investigates the differences in serotonin synthesis rates between males and females in the human brain using positron emission tomography (PET). The method involves measuring the uptake of α-11C[methyl-L-tryptophan, a tracer that is converted to α-11C[methylserotonin, which accumulates in serotonin neurons. The study found that serotonin synthesis rates were significantly higher in males (52% higher) than in females, despite uniform rates of synthesis throughout the brain. This difference may be related to the lower incidence of major unipolar depression in males. The study also demonstrated that acute tryptophan depletion (ATD) significantly reduced serotonin synthesis rates in both sexes, but the reduction was more pronounced in females. The results suggest that gender differences in serotonin synthesis could be influenced by factors such as early serotonergic events in brain organization or effects of circulating gonadal hormones. The findings raise questions about the mechanisms underlying these differences and their implications for mental health.This study investigates the differences in serotonin synthesis rates between males and females in the human brain using positron emission tomography (PET). The method involves measuring the uptake of α-11C[methyl-L-tryptophan, a tracer that is converted to α-11C[methylserotonin, which accumulates in serotonin neurons. The study found that serotonin synthesis rates were significantly higher in males (52% higher) than in females, despite uniform rates of synthesis throughout the brain. This difference may be related to the lower incidence of major unipolar depression in males. The study also demonstrated that acute tryptophan depletion (ATD) significantly reduced serotonin synthesis rates in both sexes, but the reduction was more pronounced in females. The results suggest that gender differences in serotonin synthesis could be influenced by factors such as early serotonergic events in brain organization or effects of circulating gonadal hormones. The findings raise questions about the mechanisms underlying these differences and their implications for mental health.