A number of software analysis packages for the design of PCR primers are available for PCs; however, software for users that depend on VAX/VMS operating systems is not available. By treating oligonucleotides as RNA molecules, I have designed an alternative means toward studying oligonucleotide interactions using software that is currently available from The Genetics Computer Group (GCG, Madison, WI). The oligonucleotide interactions with self and non-self are analyzed by the GCG FOLD program, a program which finds a secondary structure of minimum free energy for an RNA molecule. This approach allows the identification of self-priming primer pairs, and the interaction energies provide a guideline for the prediction of optimal PCR primers.