The actions of the α1-adrenoceptor antagonist tamsulosin have been examined at functional α1-adrenoceptor subtypes and compared with those at the human prostate receptor. At the α1D-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pKB=10.1). At the α1B-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pKB=8.9–9.2). Tamsulosin acted as an insurmountable antagonist of the α1A-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nm. Responses of depolarized (100 mm KCl) rat vas deferens preparations were unaffected by 10 nm tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. When longer antagonist incubation periods (⩾60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pKB=10.0) than obtained at the α1B-adrenoceptor. The data demonstrate that tamsulosin is a high-affinity antagonist at functional α1-adrenoceptors with a selectivity α1D⩾α1A>α1B. In some tissues, the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.