 With the recent advent of selective estrogen receptor modulators, in particular raloxifene hydrochloride, there is the potential to harness the positive estrogenic effect on CNS neurotransmitter systems without affecting breast or uterine tissue. While the CNS effects of raloxifene have not been fully studied, its actions are mediated through binding to estrogen receptors and can thereby regulate gene expression that is ligand, tissue or gene specific. By inference then, raloxifene would be expected to impact on dopamine and serotonin pathways in a similar fashion to conjugated estrogen. A study Nickleisen et al 1999 on the effect of raloxifene on cognition in healthy, postmenopausal women found a slight increase in verbal memory performance after one month of high dose treatment, while no other differences were found after 12 months of treatment. There are no studies in women with cognitive impairment where a treatment effect would be more likely to be apparent. Similarly, there are no clinical studies to date investigating the effect of raloxifene on psychotic symptoms. To this end, we are putting forward an investigator initiated clinical trial proposal to investigate the effect of adjunctive raloxifene on psychotic symptoms in women with schizophrenia. 