The unbound fraction of many drugs appears to be the therapeutically active component. However, the major problem encountered in following unbound serum gold (UBSG) concentration during chrysotherapy has been the ability to quantitate such a small quantity of gold reliably without matrix interference. The methodology detailed here overcomes these difficulties and provides an effective means of monitoring the UBSG fraction during chrysotherapy. We have observed that the unbound fraction of gold dissipates quickly after gold sodium thiomalate administration and constitutes less than 2% of the total serum gold concentration.