Similarities and differences in the actions of alcohols, barbiturates and benzodiazepines on GABA-activated chloride channels are reviewed. This question has been approached using behavioral measures, the uptake of 36Cl- by isolated brain membranes and the function of GABA-activated chloride channels expressed in Xenopus oocytes using brain mRNA. Although drugs from all three classes augment GABA-dependent chloride conductances, there are a number of differences between these drugs. Studies of genetic differences in sensitivity to sedative drugs and development of tolerance and cross-tolerance between these drugs indicate that actions of ethanol are similar (but not identical) to those of benzodiazepines but are quite different from those of pentobarbital.