Photophysical properties of semiconductor nanocrystal quantum dots (QDs) are primary determinants of their efficacy as fluorescence probes in biological systems. Our minimally passivated core/shell/shell QDs are smaller than the QDs with thick polymer coats that are often used for cellular probes, permitting less restricted access to intracellular compartments and at the same time a greater sensitivity to environmental conditions. We report here a reversible photoinduced fluorescence enhancement (photoactivation) of endocytosed mercaptoacetic-acid-capped CdSe quantum dots (MAA QDs) and the pH dependence of MAA QD photoluminescence in SKOV-3 human ovarian cancer cells. The fluorescence emission of MAA QDs taken up directly by SKOV-3 cells without the need for extra capping ligands or permeabilization steps remains bright and stable for at least 14 days. These intracellular fluorescent nanocrystals do not colocalize with low-pH lysosomes, and the emission of the MAA QDs in fixed cell preparations is quenched by acidic buffer, suggesting that a low-pH environment in cellular vesicles quenches QD fluorescence. Photoactivation of intracellular MAA QD luminescence is dependent on the excitation energy and is related to the metabolic activity of the cells. These active interactions between cells and nanocrystals demonstrate the potential of MAA QDs as intracellular environmental sensors.