Skin cells (NHEK) take up untargeted quantum dots (QD) with surface polyethylene glycol (PEG), amines, and carboxylic acids, but the mechanisms are unknown. Time courses of QD-NHEK interactions were determined and effects of QD surface coating, temperature, culture medium supplements and inhibitors of the cell cycle and endocytosis identified. The magnitude of QD-NHEK interactions was coating dependent. Low-temperature or unsupplemented medium decreased QD-NHEK interactions. Biochemical inhibitors were identified that attenuate and potentiate QD-NHEK interactions. These results are important for understanding and controlling interactions of untargeted QD with cells.