Two cDNAs(al and a4) from rat brain cDNA libraries encode isoforms of the a subunit of the GABA/benzodiazepine receptor, which differ at 30% of their amino acid residues. Northern blot analysis and in situ hybridization histochemistry show that al and a4 mRNAs have distinct sizes and distinct regional and cellular distributions in rat brain: both mRNAs are found in the cortex and hippocampus; however, only the al mRNA is detected in the cerebellum. We injected RNA tran-‘scribed from al and a4 cDNAs into Xenopus oocytes, together with an RNA for a rat b subunit. We obtained CABA-dependent inward currents that were reversibly blocked by picrotoxin. Picrotoxin alone, applied to oocytes producing the a and p polypeptides, elicited an outward current. We suggest that these polypeptides together produce GABA-gated ion channels that can also open spontaneously.