The three human alpha adrenergic receptor subtypes, alpha 1a, alpha 1b, and alpha 1c, have been cloned, expressed in COS-7 cells, and characterized pharmacologically. Competition binding studies of several adrenergic ligands with the three human receptor subtypes reveals a distinct pharmacological profile for each receptor subtype. RNase protection analysis demonstrates that the three receptor subtypes have different patterns of distribution in human tissue. The availability of the three human alpha 1 receptor subtypes will facilitate the development of subtype-selective alpha 1 antagonists for a variety of therapeutic indications.