The simultaneous detection of arsenic and sulfur in thioarsenicals was achieved using xenon-based collision-cell inductively coupled plasma (ICP) mass spectrometry (MS) in combination with high-performance liquid chromatography. In an attempt to minimize the (16)O(16)O(+) interference at m/z 32, both sample introduction and collision-cell experimental parameters were optimized. Low flow rates (0.25 mL/min) and a high methanol concentration (8%) in the mobile phase produced a fourfold decrease in the m/z 32 background. A plasma sampling depth change from 3 to 7 mm produced a twofold decrease in background at m/z 32, with a corresponding fourfold increase in the signal associated with a high ionization surrogate for sulfur. The quadrupole bias and the octopole bias were used as a kinetic energy discriminator between background and analyte ions, but a variety of tuning conditions produced similar (less than twofold change) detection limits for sulfur ((32)S). A 34-fold improvement in the (32)S detection limit was achieved using xenon instead of helium as a collision gas. The optimized xenon-based collision cell ICP mass spectrometer was then used with electrospray ionization MS to provide elemental and molecular-based information for the analysis of a fortified sample of NIST freeze-dried urine. The 3sigma detection limits, based on peak height for dimethylthioarsinic acid (DMTA) and trimethylarsine sulfide (TMAS), were 15 and 12 ng/g, respectively. Finally, the peak area reproducibilities (percentage relative standard deviation) of a 5-ppm fortified sample of NIST freeze dried urine for DMTA and TMAS were 7.4 and 5.4%, respectively.