An automated DNA synthesis protocol (FC3) has been optimized to decrease the cost of chemical consumption by two- to threefold. Anion-exchange chromatography at pH 12.5 in a Mono Q (Pharmacia) column was used to analyze the oligonucleotides we synthesized. From these analyses, we formulated the FC3 program and a procedure by which a DNA synthesizer designer or operator can use 18-base-long homopolymers of A, G, C, and T to optimize the reaction times, reagent concentrations, solvent wash conditions, and the many steps in the synthesis cycle.