A technique is described that allows the concurrent synthesis of homol
ogous regions of separate oligonucleotides. The technique utilizes syn
thesis columns that are readily interconverted between single-chambere
d and dual-chambered The regions of the oligonucleotides that differ a
re synthesized separately with single-chamber columns, and with the si
ngle modules joined, the homologous regions synthesized simultaneously
. After synthesis, the chambers are opened separately the solid-phase-
bound oligonucleotides are placed in deprotection vials and treated as
normal. Compared with standard syntheses, no decrease in yield or oli
gonucleotide quality was observed. This technique can result in signif
icant savings in rime and reagent costs when synthesizing a series of
homologous oligonucleotides. This technique could be extended to the s
imultaneous synthesis of more than two oligonucleotides, possibly up t
o four or five oligonucleotides in an appropriate multi-chambered colu
mn.