The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them, may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation, and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of Dipalmitoylphosphatidylcholine (DPPC), Curosurf® and murine LLF on the stability of AgNWs was examined. Both the phospholipid and protein components of the LLF modified the dissolution kinetics of AgNWs, due to the formation of a lipid corona or aggregation of the AgNWs. Moreover, the hydrophilic, but neither the hydrophobic surfactant proteins nor the phospholipids, induced agglomeration of the AgNWs. Finally, the generation of a secondary population of nano-silver was observed and attributed to the reduction of Ag+ ions by the surface capping of the AgNWs. Our findings highlight that combinations of spatially resolved dynamic and static techniques are required to develop a holistic understanding of which parameters govern AgNW behavior at the point of exposure and to accurately predict their risks on human health and the environment.