Alternative splicing has been shown to generate two isoforms of the apoptosis regulator bcl-x, Bcl-xL and Bcl-xS, 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-xL and bcl-xS transcripts. Since the resulting molecule has an organisation homologous to mouse and rat Bcl-x beta we suggest calling this novel protein human Bcl-x beta. Northern blot analysis revealed that bcl-x beta mRNA is expressed in numerous cell lines. Like Bcl-xL, h-Bcl-x binds to the pro-apoptotic protein Bax, suggesting a functional activity in vivo.