Two distinct benzodiazepine receptors are solubilized differentially by various detergents. The receptor sites that resist solubilization, designated type I, are most highly concentrated in the cerebellum and corpus striatum whereas the more readily solubilized receptors, type II, are most enriched in the hippocampus. The type I receptors display higher affinity for beta-carboline esters and a triazolopyridazine whereas several benzodiazepines do not differentiate the two receptors. The type I receptors can be solubilized with 2% Triton X-100/1 M NaCl; they retain the same drug specificity as in the particulate state.