Long-acting thyroid stimulator (LATS) is a 7S (IgG) γ-globulin of unknown origin found in a large number of patients with pretibial myxedema. In this study, statistically positive responses for serum LATS activity were demonstrated in 18 (94%) of 19 patients. There was, however, a poor correlation between the severity of the skin lesions and the level of serum LATS. In all patients tested, serum immunoglobulins IgG, IgA, and IgM were within normal limits. With immunofluorescent techniques, attempts were made to demonstrate IgG, IgA, IgM, fibrinogen, and complement C'3 in affected tissues, but results were uniformly negative. No LATS response could be demonstrated from tissue extracts from areas of pretibial myxedema. These latter two findings do not support the concept of the production of pretibial myxedema as a result of a local antigenantibody tissue reaction.