The aim of this study was to investigate the ability of a series of different surface-coated quantum dots (QDs) to cause oxidative stress and affect cell signalling in J774.A1 macrophages. Organic QDs caused a significant (p < 0.001) decrease in glutathione (GSH) levels over 24 h, while COOH and NH2 (PEG) QDs induced a significant decrease (p < 0.05) in GSH at 6 and 24 h only. J774.A1 cytosolic Ca2+ concentration significantly increased (p < 0.01) 30 min after treatment with all QDs. Trolox was, however, able to prevent the COOH and NH2 (PEG) QD-induced Ca2+ signal, but not the organic QD induced effect. All QDs tested were observed to have a relatively low ability to stimulate increased expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). In conclusion, QDs differ in their interactions with macrophages according to their specific surface properties.