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DNA oligonucleotides that anneal to form duplexes in specific, planned configurations are a basic construction material for DNA-based computers and nanotechnology. Unplanned duplex configurations introduce errors in computations and defects in structures, and thus, the sequences must be designed to minimize these effects. A software design tool has been developed that uses thermodynamic models of DNA duplex thermal stability and algorithms from graph theory to select good sets of oligonucleotides. An example set was tested in the laboratory, and the designed sequences formed no unplanned duplexes and had no detectable secondary structure. © 2003 American Institute of Physics.