Using vesicles from the plasma membrane of hog thyroid, we have characterized its Na+-dependent I- transport system. We have found it to be totally Na+ dependent; K+ cannot substitute and Li+ can partially substitute for Na+; the Na+:I- flux ratio is larger than one; the system is electrogenic, being stimulated by a delta psi negative inside the vesicles. A number of large, lipophilic anions are fully-competitive inhibitors of Na+-dependent I- uptake; the closer their atomic radii are to that of iodine, the smaller their Ki values.