Ion-exchange chromatography hyphenated with mass spectrometric detection has been investigated for the determination of iodide in urine. Satisfactory chromatographic behavior of iodide could be achieved on a hydrophilic polymer-based anion-exchange column with 35 mM sodium hydroxide as the mobile phase. When electrospray ionization (ESI) was used, a suppressor as well as a flow splitter (split ratio 1∶10) was required between the column and the interface. In the case of an inductively coupled plasma (ICP) ionization source, eluent and flow-rate were completely compatible with the interface. Under comparable chromatographic conditions, the ESI interface yielded a detection limit of 15 µg L⁻¹ (quadrupole instrument), whereas the ICP interface lowered the detection limits by approximately two (quadrupole instrument) and three (sector field instrument) orders of magnitude. For urine samples both methods gave virtually the same results except for the relative standard deviation, which was 7% for ESI and 0.55% for sector field ICP. The molecule-selective detection of ESI may be an advantage in cases when insufficient separation from other iodine-containing species cannot be avoided. The element-selective ICP will be the preferred tool when iodide has to be determined in the sub-ppb range.