Iodide (I(-)) is an essential constituent of the thyroid hormones triiodothyronine and thyroxine, which are required for the development of the central nervous system in the fetus and newborn. I(-) uptake in the thyroid is mediated by the Na(+)/I(-) symporter (NIS). NIS has gained particular medical interest due to its sensitivity to the environmental pollutant perchlorate (ClO(4)(-)) and its implication in radioiodide cancer treatment. Recently, others have shown that I(-) absorption in the intestine is mediated by NIS (Nicola, J. P., Basquin, C., Portulano, C., Reyna-Neyra, A., Paroder, M., and Carrasco, N. (2009) Am. J. Physiol. Cell Physiol. 296, C654-662). However, their data suggest the participation of other systems in the homeostasis of I(-), in particular because in vivo uptake studies revealed a ClO(4)(-)-insensitive transport component. Here, we describe Na(+)-coupled I(-) uptake by the human Na(+)/multivitamin transporter (hSMVT), a related protein isolated from the placenta, where it was suggested to supply the fetus with the water-soluble vitamins biotin and pantothenic acid, and α-lipoic acid. hSMVT-mediated Na(+)/I(-) symport is inhibited by the other three organic hSMVT substrates but not by NIS substrates; notably, hSMVT is insensitive to ClO(4)(-). Because hSMVT is found in the intestine and in many other tissues, we propose that hSMVT may play an important role in the homeostasis of I(-) in the body.