This research project is a direct continuation of 20 years of investigation of the pathogenesis of hyperthyroidism. The specific, current aim is primarily the development of hybridomas secreting monoclonal thyroid-stimulating antibodies. The hybridomas will be of two types: 1. Mouse/mouse hybridoma. Preparations of human thyroid gland will be used to immunize mice whose spleen lymphocytes will then be fused with mouse myeloma cells. 2. Human/human hybridoma. Peripheral blood lymphocytes will be fused with human myeloma cells. Monitoring the hybridoma secretions will be by assessing inhibiton of 125I-labelled thyrotropin binding to preparations of thyrotropin receptors. A second major current effort is to develop the cytochemical assay of thyroid stimulators using sections of guinea pig thyroid to test biologically those monoclonal antibodies that are positive in the initial screening. Scientific displines involved: endocrinology; immunology. Health relatedness: increased understanding of Graves' Disease and the autoimmune disorders in general.