Lead selenide nanoclusters and nanocubes were successfully prepared on the eggshell membrane (ESM) through a room-temperature-biosubstratedirected approach. The nanoclusters were assembled by fine nanocrystallites, while single-crystalline nanocubes came into being through a ripen progress, and obtained lead selenide nanocrystallites were distributed homogeneously over the whole ESM. The morphology and the size were governed mainly by the configuration and chemical functional residues of the ESM and the synthesis conditions as well as their reciprocities. The functional groups such as amido groups and imido residues of the ESM macromolecules could not only direct the formation of 4-7 run PbSe nanocrystallites and the assembly into nanoclusters and nanocubes, but act as a surfactant to well-distributed fine PbSe nanocrystallites. The as-prepared nanocrystalline PbSe exhibited single-crystalline, small-scaled and well-dispersed performances, which would offer more potential applications in semiconductors, lasers, optoelectronic devices and the like nanoelectronic fields. (c) 2006 Elsevier B.V. All rights reserved.