Competition analyses with a number of known bioflavonoids and related compounds revealed that three of them competed effectively for type II [ 3H]estradiol-17β ([ 3H]E 2) binding sites (type II sites) in the nuclei of rat dorsolateral prostate (DLP). Amongst the bioflavonoids tested, quercetin was the most effect, exhibiting approx. a 50% inhibition at 3000-fold molar excess concentration. In contrast, rutin and hesperitin were both not effective. Methyl p-hydroxyphenyllactate (MeHPLA), a suspected “endogenous” ligand for uterine type II sites [1; J. Biol. Chem. 263, 1988, 7203–7210], competed as well as estradiol-17β (E 2) for prostatic type II sites (50% inhibition at 30-fold molar excess), whereas its demethylated product, HPLA, did not. 4,4'Dihydroxybenzylidene acetophenone, an esterase-stable MeHPLA analog, was also found to be a good competitor, exhibiting a 50% inhibition at 100-fold molar excess concentration. In a preliminary in vivo study, quercetin, administered either orally or subcutaneously, was found to be effective in preventing a joint testosterone (T) and E 2 treatment-induced elevation of type II sites in rat DLP. Quercetin treatments also caused a small but significant reduction (17–18%) in DLP relative gland weights (gland wt/body wt) in T + E 2-treated animals. Taken together, these data suggest that bioflavonoids and related compounds may influence prostatic function via interactions with prostatic type II sites.