Binding activity for the cage convulsant [35S]-tert- butylbicyclophosphorothionate , which appears to label a site closely associated with the chloride ionophore of the GABAA /benzodiazepine receptor complex has been solubilized from rat cerebral cortex using the zwitterionic detergent CHAPS . Of several detergents screened, only CHAPS and CHAPSO were capable of solubilizing the binding activity with good recovery. The pharmacologic specificity of soluble [35S]-tert- butylbicyclophosphorothionate binding is very similar to the membrane state. In both the membrane and soluble state, [35S]-tert- butylbicyclophosphorothionate binding is enhanced by anions which support inhibitory post-synaptic potentials (" Eccles anions"), suggesting that [35S]-t- butylbicyclophosphorothionate may label chloride channels though to be involved in these potentials. Since this solubilization procedure also preserves GABA and benzodiazepine binding and their regulation by drugs such as barbiturates, purification and isolation of the macromolecular complex including chloride channel and GABA-benzodiazepine sites may be feasible.