The effects of phytoestrogens on neuronal nicotinic acetylcholine receptor/channels were examined by expressing recombinant channels in Xenopus oocytes. When functional channels were expressed with human alpha4 and beta2 subunits, daidzein (10 and 100 microM) partially inhibited the ionic current activated by acetylcholine. The current inhibition was also observed when functional channels were expressed with human alpha3 and beta4 subunits or rat homologues. Genistin (100 microM) also inhibited the acetylcholine-activated current. Tamoxifen (100 microM), an antiestrogen did not antagonize the inhibition by daidzein. The results suggest that phytoestrogens, like estrogens and xenoestrogens, block human neuronal acetylcholine receptors through non-genomic mechanisms.