Here we report on the seemingly simple process of galvanic exchange (GE) between electrogenerated AuCl4- and silver nanoparticles (AgNPs). The results were obtained in the specific context of using AgNPs as labels for bioassays in paper fluidic devices. Results obtained from a combined electrochemistry and microscopy study indicate that the GE process results in recovery of only ∼5% of the total equivalents of Ag present in the system. This low value is a consequence of two factors. First, after an initial fraction of each AgNP undergoes GE, a Au shell forms around the remaining AgNP core preventing further exchange. Second, to simulate a true biological fluid, the experiments were carried out in a Cl--containing buffer. Consequently, some Ag+ formed during GE precipitates as AgCl, and it also serves to block additional GE. Following optimization of the GE process, it was possible to detect AgNP label concentrations as low as 2.6 fM despite these limitations.