Nucleic-acid-functionalized CdSe/ZnS quantum dots (QDs) were hybridized with the complementary Texas-Red-functionalized nucleic acid. The hybridization was monitored by following the fluorescence resonance energy transfer from the QDs to the dye units. Treatment of the QD/dye DNA duplex structure with DNase I resulted in the cleavage of the DNA and the recovery of the fluorescence properties of the CdSe/ZnS QDs. The luminescence properties of the QDs were, however, only partially recovered due to the nonspecific adsorption of the dye onto the QDs. Similarly, nucleic-acid-functionalized An nanoparticles (An NPs) were hybridized with the complementary Texas-Red-labeled nucleic acid. The hybridization was followed by the fluorescence quenching of the dye by the Au NPs. Treatment of the An NP/dye DNA duplex with DNase I resulted in the cleavage of the DNA and the partial recovery of the dye fluorescence. The incomplete recovery of the dye fluorescence originated from the nonspecific binding of the dye units to the An NPs. The nonspecific binding of the dye to the CdSe/ZnS QDs and the Au NPs is attributed to nonprotected surface vacancies in the two systems.