Iodoalbumin has been found in the goiter of Dutch goats with a thyroglobulin synthesis defect. Immunohistochemical studies showed that in the goiter the percentage of follicles containing albumin was higher than that in normal thyroid glands. In the albumin-containing follicles of normal and goitrous glands, transferrin and immunoglobulin G could be found. Also, between the epithelial cells, serum proteins were detected. These results indicate intercellular passage of serum proteins. After in vivo labeling with 125I, goiter slices were incubated with [3H] leucine. Purified 125I-containing albumin did not contain [3H]leucine, while thyroglobulin antigens were double labeled. Cyanogen bromide treatment of albumin out of the goiter and of serum albumin gave comparable cleavage patterns, indicating that no great differences in amino acid composition, especially methionine, exist. In total RNA from goiter, no albumin mRNA could be detected after blotting and hybridization with goat albumin cDNA. Also, the polymerase chain reaction method with albumin DNA primers was unable to detect any albumin mRNA in normal and goitrous glands of goats. From these results we conclude that "thyralbumin" originates from blood and is not synthesized by the thyroid gland.