A mast cell/fibroblast co-culture system is used as a model to assess the toxicity of Au nanoparticles over the course of 72 hours of exposure. Cellular uptake of nanoparticles was found to increase over the 72 hr exposure period and the nanoparticles localized within granular bodies of the primary culture mast cells. These granules were found to increase in volume with the addition of nanoparticles. There was no decrease in viability for 24 hr exposed cells but a slight viability decrease was found after 48 and 72 hr exposure. Carbon-fiber amperometry analysis of exocytosis of serotonin from mast cells revealed changing release profiles over the time course of exposure. In early exposure times, granular secretion of serotonin increased with exposure to Au nanoparticles whereas 72 hr exposure showed decreased secretion of serotonin with nanoparticle exposure. The kinetics of this release was also found to be affected by Au colloid exposure where the rate of serotonin expulsion decreased with increasing nanoparticle exposure. These results illustrate the dynamic nature of nanoparticle-cell interactions and the critical changes in cell behavior even when viability is unaffected.