Abstract: A procedure involving directly coupled HPLC-ICP-MS is described for the quantification of metals associated with cytosolic proteins. Selectivity is achieved by sequential fractionation by size exclusion (TSK SW2000) followed by ion exchange chromatography (Showdex DEAE). Spectra on up to 11 masses for six elements were acquired simultaneously by scanning the quadrapole in the peak hopping mode. A flow injection loop inserted downstream of the columns was used to monitor analyte recovery and quantify the ion intensity profiles from the MS. Reproducibility of analysis was approximately 2-5% and absolute detection limits were typically between 10 and 60 pg of analyte. The utility of the technique for: (i) detecting abnormal distributions in cytosolic metals due to metal exposure; and (ii) determining the biological turnover of Cu and other metals associated with proteins is demonstrated using the marine shellfish Littorina littorea exposed to elevated concentrations of Cd and 65Cu.