Many of the depressant effects caused by alcohol are believed to stem from an enhancement of inhibitory neurotransmission in the central nervous system, specifically the enhancement of GABAA and glycine receptor function. Glycine receptor modulators include a wide variety of chemical compounds including drugs of abuse like alcohol and inhalants, as well as clinically used drugs like volatile anesthetics and pentobarbital. While it is known that these modulators enhance glycine receptor-mediated currents, more specific molecular mechanisms have eluded us. By studying a glycine receptor that activates in the absence of neurotransmitter but retains its ability to be modulated by alcohol, new insights into activation mechanisms could be discovered. A better understanding of ligand-gated ion channel receptor mechanisms could lead to therapeutic agents such as alcoholism treatment regimens and anesthetics with fewer side effects. The work proposed may not only shed insights into the molecular mechanisms of ethanol and other receptor modulators, but also provide a fuller understanding of basic receptor/channel processes.