Brain serotonin functional variation is implicated in a range of heritable diseases including alcoholism, mood disorders, eating and obsessive-compulsive (OCD) disorders. An important starting point for understanding innate vulnerability to such diseases is to identify variation in genes involved in serotonin function. The 5-HT2A receptor gene is thought to contribute to appetitive behaviors and to anxiety, and is one site of action of antipsychotics, hallucinogens and anti-depressants. 5-HT2A receptor densities are higher in individuals with depression and suicide attempts. In this study we replicated an earlier finding of an association of the 5-HT2A promoter polymorphism -1438G/A with anorexia nervosa. In addition we showed that the association extends to OCD but not to bulimia nervosa, a disorder in which obsessive and perfectionist traits are less manifest (Enoch et al 1998). We have now shown that the promoter polymorphism is associated with OCD in women but not men (Enoch et al 2001). We have also shown an association of the -1438A variant allele with Seasonal Affective Disorder, a condition in which depression recurs in the winter and remits in the spring (Enoch et al 1999). Association studies are being completed in other data sets and preparations are being made for functional studies of this promoter polymorphism. The 5HT2C receptor is widely expressed in brain where it is involved in the regulation of endocrine responses and serotonin and norepinephrine activity. This receptor is thus a candidate gene for several neuropsychiatric disorders, including alcoholism and anxiety disorders. A 5' exonuclease assay has been designed for the functional 5HT2C Cys23/Ser23 polymorphism. This assay will be used for genotyping large populations in the near future.