Serum protein binding of thyroid hormone (125I-T4) and the frequency of occurrence of circulating thyroid autoantibodies were studied by conventional electrophoretic and serological techniques in 599 obese and 150 nonobese subjects from the Louisville area, as well as in 145 nonobese individuals from a different population. In the sera of 7.3% of obese individuals tanned red cell agglutinating thyroid autoantibodies were present. Aberrations in the serum protein binding of thyroid hormone as well as altered electrophoretic mobilities of alpha and beta globulins were seen in 4.3% of the obese population, and within the latter 30.8% of the sera contained thyroid autoantibodies; anomalous serum thyroxine binding was also observed in 2 apparently normal individuals. The predominant aberration as noted in paper electrophoretograms consisted in the binding of 125I-T4 primarily at alpha 2-beta globulin rather than at interalpha TBG. The specificity of aberrant thyroid hormone-protein interaction was established by various control procedures. The characteristics of this unusual thyroxine binding protein, save for the slightly reduced electrophoretic mobility, were similar to TBG of normal human serum, and hence the aberrant thyroxine binding protein was termed slow-moving TBG. Clinical and laboratory tests of patients who had slow-moving TBG in the circulation did not indicate abnormality of thyroid gland function. Aberrant serum protein binding of 125I-T4 as well as alterations in the mobilities of protein bands, analogous to that noted in the sera of some obese individuals as described above, were also seen in normal human serum treated with sialidase in vitro in both paper and gel electrophoretic systems.