The projected use of oligonucleotides and their analogs as antisense and antigene therapeutic agents has created a need for efficient methods for their synthesis. Currently available system using batch, vortex, or column reactors are inherently incapable of efficient operation at the preparative scale desired (100 millimole or larger). This grant proposes the development of novel synthesis reactor architecture coupled with a new highly economical solid support to provide a practical means for the preparation of ODN's at the 100g to 1 KG scale. The instrumental design will allow the execution of all available chemistries at the highest possible efficiency.