Abnormally high plasma thyrotropin values were found by radioimmunoassay in some patients when an antiserum to porcine thyrotropin was used, normal results being obtained with an antiserum raised to human thyrotropin. These discrepancies were found in some subjects with no biochemical or clinical evidence of hypothyroidism and occasionally in sera from patients with unequivocal hyperthyroidism. We found a substance in serum that cross reacts with the anti-porcine antiserum, is stable on repeated freezing and thawing, and is independent of the 125I-labeled tracer preparation. It is unlikely that this substance is a separation-stage artefact related to immunoglobulins. Its apparent molecular weight (gel filtration) is 114 000, as compared with apparent molecular weights for standard thyrotropin and endogenous thyrotropin (as found in idiopathic hypothyroidism) of 34 700 and 38 000, respectively. We believe the substance is a normal serum constituent that is present in large quantities in a minority of subjects. Apparently unrelated to TSH, its exact chemical nature remains unidentified.