The species-specificity of thyrotrophin binding inhibitor immunoglobulin (TBII) for the thyroid TSH receptor was investigated using a preparation of thyroid plasma membranes (TPM) from propylthiouracil-treated mice, as well as from human glands. The interest in the mouse arose from its use as the bioassay animal for the long-acting thyroid stimulator (LATS). A comparison was made of the response in the two radioreceptor assays of serum immunoglobulins from ten normal subjects and twenty patients with Graves's disease, who had also been selected to have positive TBII activity in the assay based on human TPM. All the specimens from the patients with Graves's disease had detectable TBII activity in the mouse radioreceptor assay, inhibiting the binding of 125I-labelled TSH to a greater extent than did any of the specimens from normal subjects. There was evidence for a minor degree of species-specificity, since at least one of the specimens from the Graves' disease group had unexpectedly high activity in the assay based on mouse TPM and another had unexpectedly weak activity in that assay. However, this specificity appeared to be unrelated to the presence or absence of LATS. The effect of LATS on the response of serum immunoglobulins in the mouse radioreceptor assay was tested using nine patients with Graves's disease who had undetectable serum LATS and another eight patients with Graves's disease whose serum gave a positive LATS response. These patients had also all been selected to have positive TBII activity in their serum, as determined with human TPM. All samples from each of the LATS-positive and LATS-negative subgroups gave a positive TBII response in the radioreceptor assay based on mouse TPM, and there was extensive overlap between the individual values for the two subgroups. It is concluded that the failure of some TBII-positive serum immunoglobulins to stimulate the mouse thyroid gland and produce a positive LATS response is not due to species-specificity at the level of receptor binding.