Most of the evidence to support an association between estrogen and psychosis is indirect and comes from clinical studies of gender differences in schizophrenia and from studies of fluctuating levels of psychopathology in different phases of the menstrual cycle. Our data, as well as those of other investigators, suggest a significantly later age at onset of schizophrenia in women than in men. There is somewhat more direct evidence from animal studies indicating that estrogen modulates dopamine systems in a manner similar to neuroleptics, although there are some inconsistencies in the literature. Few studies have examined the effects of estrogen administration in conjunction with neuroleptics on psychotic symptoms. We present a case report of a postmenopausal women with schizophrenia who had an improvement in positive symptoms with estrogen replacement therapy. Long-term double-blind treatment studies are needed to investigate the effects of estrogen on psychotic symptoms in women with schizophrenia.