The benzodiazepines were introduced into clinical practice in 1960 and since that time have become one of the most frequently prescribed of all psychotropic agents. Over the past 25 years the mechanism by which these compounds produce their effects has been revealed by a combination of electrophysiological and biochemical studies. It is now apparent that these drugs interact with a specific recognition site on the GABAA receptor complex and thereby modulate the gating of the chloride channel associated with this major inhibitory amino acid transmitter receptor. This modulation is novel in that while the clinically prescribed benzodiazepines increase the chloride current in response to a given GABA stimulus, agents are now known which produce the opposite effect. However, the details of the molecular mechanisms by which these events occur remain to be elucidated. Our progress toward this goal will rely on the acquisition of structural information about this receptor protein using the techniques of molecular biology and its marriage with new initiatives concerning the detail of ligand recognition. The interpretation of such information in the context of the complex pharmacology of this important receptor system is indeed a stimulating prospect.