Water-soluble gold nanoparticles (AuNPs) have gained considerable attention because they offer a myriad of potential applications, especially in the fields of biology and medicine. One method to prepare such gold nanoparticles is through the well-known Murray place-exchange reaction. In this method, precursor gold nanoparticles, bearing labile ligands and with very good size distribution, are synthesized first, and then reacted with a large excess of the desired ligand. We report a comparison of the reactivity of several known precursor gold nanoparticles (citrate-stabilized, pentanethiol-stabilized, tetraoctylammonium bromide-stabilized, and 4-dimethylaminopyridine-stabilized) to several biologically relevant ligands, including amino acids, peptides, and carbohydrates. We found that citrate-stabilized and 4-dimethylaminopyridine-stabilized gold nanoparticles have broader reactivities than the other precursors studied. Citrate-stabilized gold nanoparticles are more versatile precursors because they can be prepared in a wide range of sizes and are very stable. The hydrophobic pentane-stabilized gold nanoparticles made them "inert" toward highly water-soluble ligands. Tetraoctylammonium bromide-stabilized gold nanoparticles exhibited selective reactivity, especially for small, unhindered and amphiphilic ligands. Depending on the desired ligand and size of AuNPs, a judicious selection of the available precursors can be made for use in place-exchange reactions. In preparing water-soluble AuNPs with biologically relevant ligands, the nature of the incoming ligand and the size of the AuNP should be taken into account in order to choose the most suitable place-exchange procedure. Published by Elsevier Inc.