Alternative splicing has been shown to generate two isoforms of the apoptosis regulator bcl-x, Bcl-x_Land Bcl-x_S, in humans. Here we describe the identification and characterization of a third splice variant of the human bcl-x gene. It differs from previously described bcl-x transcripts in two respects: (1) a novel facultative intron is spliced out at the 5′ untranslated region and (2) the open reading frame arises from a continuous genomic sequence extending over the splice donor sites utilized by the bcl-x_Land bcl-x_Stranscripts. Since the resulting molecule has an organisation homologous to mouse and rat Bcl-x_βwe suggest calling this novel protein human Bcl-x_β. Northern blot analysis revealed that bcl-x_βmRNA is expressed in numerous cell lines. Like Bcl-x_L, h-Bcl-x_βbinds to the pro-apoptotic protein Bax, suggesting a functional activity in vivo.