Genetic variants have been discovered in two genes encoding for tryptophan hydroxylase (TPH)-TPH1 and TPH2. Low tryptophan (TRP) levels are associated with depression and may arise because of stress. Evidence suggests that hypothalamic and peripheral 5HT systems have a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels.We examined the association between a polymorphism in intron 7 of TPH1, 218A>C and plasma total TRP levels in 118 patients with major depression.There was an interaction between 218A>C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP.The study investigated only the TRP1 gene and did not use a haplotype analysis. The results only apply to a population of subjects suffering from major depression.TPH1 may be associated with the regulation of peripheral tryptophan levels and therefore availability of tryptophan to the brain. This may have relevance to a range of neuropsychiatric conditions.