Metal-enriched metal sulfide nanoparticles (MS-M2+, M = Zn, Cu, Pb, Ni, Cd) have been prepared. We found ZnS-Zn2+ and CuS-Cu2+ nanoparticles are water-soluble and biocompatible. They could be used as new kind of resonance light-scattering (RLS) probes in the determination of gamma-globulin human, which was proved to be a simple, rapid and specific method. In comparison with organic dye probes, these nanoparticles probes are brighter, more stable against photobleaching, and do not suffer from blinking. Under the optimum conditions, the response is linearly proportional to the concentration of gamma-globulin human. ZnS-Zn2+ nanoparticles as a RLS probe: between 0.1 and 2.0 mg l(-1), and the limit of detection is 0.0403 mg l(-1); CuS-Cu2+ nanoparticles as a RLS probe: between 0.1 and 1.5 mg l(-1), and the limit of detection is 0.0646 mg l(-1). We find the effect of other protein on this assay is weak, this assay has good selectivity.