The study was designed to examine the effects of thyroid hormones on red blood cell (RBC) membrane phospholipids and ion transport. We demonstrated that in untreated Graves' disease, an alteration in the phospholipid pattern is present at cellular levels, with a concomitant derangement in membrane permeability defined as (22)Na influx and (45)Ca uptake. Thionamide therapy replaced the normal membrane permeability, presumably as a consequence of restoring the normal phospholipid membrane composition. We conclude that thyroid hormones are able to induce a quick breakdown of a large number of membrane components such as membrane phospholipids.