Oestrogen, a sex steroid hormone, has long been hypothesized to be involved in alterations to pathways involved in neurotransmission, and therefore may be involved in neuropsychiatric conditions including bipolar disorder. Indeed, certain depressive disorders in women have been found to be associated with low levels of oestrogen and can be much improved by the administration of this hormone. As the effects of oestrogen are most probably mediated through the oestrogen receptors (ER alpha and ER beta), the genes encoding these receptors may be possible candidates for association studies with bipolar disorder and other neuropsychiatric disorders. A number of studies, including previous results from this group, have reported modest evidence of linkage between both bipolar disorder and schizophrenia and a region of chromosome 14 (q22-q24), where the ER beta gene has been localized. In the present study, a sample of 102 Irish parent-proband trios were genotyped for a single nucleotide polymorphism within the ER beta gene (3' untranslated region, A1730G). However, the transmission/disequilibrium test failed to reveal evidence of a distortion in allele transmission to bipolar I (BPI) probands.