A number of (S)- and (R)-2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes unsubstituted or ortho monosubstituted at the phenoxy moiety were synthesized and tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR and the 5-HT(1A) receptor. The affinity values of the new compounds 1-16 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha(1) antagonist WB4101, finding that the unsubstituted derivative (S)-1 and the o-methyl, the o-t-butyl, the o-fluoro and the o-methoxy derivatives, (S)-2, (S)-4, (S)-8 and (S)-16, respectively, display a significantly specific 5-HT(1A) affinity, very close, with the exception of (S)-4, to the almost nanomolar one of (S)-WB4101. Otherwise, sensible affinity decreases were recorded for the three alpha(1)-AR subtypes. A classical quantitative structure-activity relationship (Hansch) analysis was successfully applied to compounds (S)-1 to (S)-16 and (S)-WB4101 to rationalize such binding data.