The α subunit of the guanine nucleotide-binding protein G(o) ('o' for other) is believed to mediate signal transduction between a variety of receptors and effectors. cDNA clones encoding two forms of G(o) α subunit were isolated from a mouse brain library. These two forms, which we call G(o)Aα and G(o)Bα, appear to be products of alternative splicing. G(o)Aα differs from G(o)Bα over the C-terminal third of the deduced protein sequence. Both forms are predicted to be substrates for ADP-ribosylation by pertussis toxin. G(o)Aα transcripts are present in a variety of tissues but are most abundant in brain. The G(o)Bα transcript is expressed at highest levels in brain and testis. It is possible G(o)Aα and G(o)Bα have different functions.