Opiate drug responses are mediated through a specific interaction of the drug with the opioid receptor which is membrane bound in various tissues. The proposed study will purify and concentrate antibodies which combine with the receptor and in turn utilize these antibodies as probes of opioid receptor structure and function. The antibodies will be generated in animals by means of an unique immune technique which involves the formation of anti-idiotypic antibodies. Purified antimorthine antibodies obtained from rabbits will be utilized as the antigen and following immunization with this antigen in mice, a second set of antibodies (anti-idiotypic antibodies) will be produced which may recognize and combine with the opiate receptor. The antiopioid receptor antibodies will be purified and their influence on opioid receptor binding in brain homogenates and opiate response in the isolated guinea pig ileum will be characterized. Monovalent and bivalent antibody fragments will be prepared and used to elucidate the role of opioid receptor microaggregation and cross-linking in mediating narcotic drug responses such as opiate tolerance and addiction.