α₁-Adrenoceptor antagonists are clinically useful for the improvement of urinary obstruction due to benign prostatic hyperplasia (BPH), and their therapeutic effects are mediated through the blockade of prostatic α₁-adrenoceptors. The present study was undertaken to predict the magnitude and duration of α₁-adrenoceptor occupancy in the human prostate after oral α₁-adrenoceptor antagonists. Prostatic α₁-adrenoceptor-binding parameters of silodosin were estimated by measuring specific [³H]prazosin binding in rat prostate after oral administration of this drug. The plasma concentration of silodosin after oral administration in rats and healthy volunteers was measured using a high-performance liquid chromatographic method. The α₁-adrenoceptor-binding affinities (K_i) of silodosin, tamsulosin, and terazosin in the human prostate and plasma concentrations of tamsulosin and terazosin were obtained from the literature. Using the α₁-adrenoceptor binding parameters of silodosin in rat prostate, α₁-adrenoceptor occupancy in the human prostate was estimated to be around 60—70% at 1—6 h after oral administration of silodosin at doses of 3.0, 8.1, and 16.1 μmol. Thereafter, the receptor occupancy was periodically decreased, to 24% (8.1 μmol) and 54% (16.1 μmol) 24 h later. A similar magnitude and time course of α₁-adrenoceptor occupancy by silodosin in the human prostate were estimated using α₁-adrenoceptor-binding affinities (K_i) in the human prostate. Despite about two orders of differences in the plasma unbound concentrations after clinically effective oral dosages of silodosin, tamsulosin, and terazosin, there was a comparable magnitude of prostatic α₁-adrenoceptor occupancy by these drugs. In conclusion, the prediction of α₁-adrenoceptor occupancy in the human prostate by α₁-adrenoceptor antagonists may provide the rationale for the optimum dosage regimen of these drugs in the therapy of BPH.