Much evidence supports the view that the α-adrenoreceptor is not a homogeneous entity, with classical postsynaptic α₁ (initiating effector organ response) and presynaptic α₂ (modulating neurotransmitter release via feedback) subtypes, though this classification is not absolute as subtypes can be found in other regions. Selective ligands are needed to characterize α-adrenoreceptor subtypes. Benzodioxans, a class of α-adrenoreceptor antagonists, led to the discovery of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxan (WB 4101, 2), a potent and selective α₁-antagonist widely used for characterization, but its potency and selectivity have not been improved until now. We report the synthesis and preliminary characterization of a new antagonist, 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzoxathian hydrochloride monohydrate (1). In isolated rat vas deferens, 1 showed competitive action at both subtypes, high α₁ potency (pA₂ 9.26 vs. 8.83 for 2 and 8.74 for prazosin) and unprecedented α₁/α₂ selectivity (ratio 1000 vs. 347 for 2 and 851 for prazosin). This is the first structural manipulation of 2 increasing α₁ affinity. Compound 1 is a potent and selective α₁-adrenoreceptor antagonist that may represent a valuable tool in the characterization of α-adrenoreceptor subtypes.