At synapses, a transmitter released from a pre-synaptic terminal binds to specific, ligand-gated receptors in the post-synaptic membrane to open up ion channels through the receptor molecules. The flow of ions through these channels generates electrical signals. Electrophysiological techniques have been used over the past 50 years to understand transmission of these signals at synapses. The most recent of these, the patch-clamp technique, allows very small picoamp currents through single-channel molecules to be recorded but gives little information about receptor structure or how drugs influence their function. Now, the subunits of most ligandgated ion channels have been cloned and sequenced. Cryo-electronmicroscopy has revealed the structure of the ion channel activated by nicotinic agonists. It is pentameric and only a small part of it is in the membrane. In spite of this simple structure, the conductance of chloride channels activated by gamma-aminobutyric acid (GABAA channels) is very variable and can be increased markedly by drugs such as diazepam. Site-directed mutagenesis and labelling of cysteine residues in the open and the closed states are being used to define the residues that line the ion channel. Similar methods are being used to find the way in which drugs such as general anaesthetics modulate the function of GABAA receptors.