The glycine receptor is a ligand-gated anion channel protein, providing inhibitory drive within the nervous system. We report here the isolation and functional characterization of a novel alpha subunit (alphaZ1) of the glycine receptor from adult zebrafish (Danio rerio) brain. The predicted amino acid sequence is 86%, 81% and 77% identical to mammalian isoforms alpha1, alpha3 and alpha2, respectively. AlphaZ1 exhibits many of the molecular features of mammalian alpha1, but the sequence patterns in the M4 and C-terminal domains are more similar to alpha2/alpha3. Phylogenetic analysis indicates that alphaZ1 is more closely related to the mammalian alpha1 subunits, being positioned, however, on a distinct branch. The alphaZ1 messenger RNA is 9.5 kb, similar to that described previously for alpha1 messenger RNAs. When expressed in Xenopus oocytes or a human cell line (BOSC 23), alphaZ1 forms a homomeric receptor which is activated by glycine and antagonized by strychnine. This receptor demonstrates unexpectedly high sensitivity to taurine and can also be activated by GABA. These results are consistent with physiological findings in lamprey and goldfish, and they suggest that this teleost fish glycine receptor displays a lower selectivity to neurotransmitters than that reported for glycine mammalian receptors.