The development of nanoparticles (NPs) for commercial products is undergoing a dramatic expansion.Many sunscreens and cosmetics now use zinc oxide (ZnO) or titania (TiO2) NPs, which are effectiveultraviolet (UV) filters. Zinc oxide topical creams are also used in mild anti-inflammatory treatments. Inthis study we evaluated the effect of size and dispersion state of ZnO and TiO2NPs, compared to “bulk”ZnO, on mast cell degranulation and viability.ZnO and TiO2NPs were characterized using dynamic light scattering and disc centrifugation. Ratbasophilic leukaemia (RBL-2H3) cells and primary mouse bone marrow-derived mast cells (BMMCs)were exposed to ZnO and TiO2NPs of different sizes (25–200 nm) and surface coatings at concentrationsfrom 1 to 200 g/mL. The effect of NPs on immunoglobulin E (IgE)-dependent mast cell degranulationwas assessed by measuring release of both -hexosaminidase and histamine via colorimetric and ELISAassays. The intracellular level of Zn2+and Ca2+ions were measured using zinquin ethyl ester and Fluo-4 AMfluorescence probes, respectively. Cellular viability was determined using the soluble tetrazolium-basedMTS colorimetric assay.Exposure of RBL-2H3 and primary mouse BMMC to ZnO NPs markedly inhibited both histamine and-hexosaminidase release. This effect was both particle size and dispersion dependent. In contrast, TiO2NPs did not inhibit the allergic response. These effects were independent of cytotoxicity, which wasobserved only at high concentrations of ZnO NPs, and was not observed for TiO2NPs.The inhibitory effects of ZnO NPs on mast cells were inversely proportional to particle size and disper-sion status, and thus these NPs may have greater potential than “bulk” zinc in the inhibition of allergicresponses.