Factors influencing the direct transformation of the yeast Saccharomyces cerevisiae with synthetic oligonucleotides were investigated by selecting for cyc1 transformants that contained at least partially fuctional iso‐1‐cytochrome c. Aproximately 3 × 10⁴ transformanrs, constituting 0·1% of the cells, were obtained by using 1 mg of oligonucleotide in the reaction mixture. Carrier, such as heterogenous oligonucleotides, enhanced transformation frequencies. Transformation frequencies were dramatically reduced if the oligonucleotides had a large number of mismatches or had terminally located mismatches. Transformation with oligonucleotides, but not with linearized double‐strand plasmid, was efficient in a rad52⁻ strain, ssuggesting that the pathway for transformation with oligonucleotides is different from that with linearized double‐strand plasmid. We describe a procedure of co‐transformation with two oligonucleotides, one correcting the cyc1 defect of the target allele in the host strain, and the other producing a desired amono acid alteration elsewhere in the iso‐1‐cytochrome c molecule; approximately 20% of the transformants obtained by co‐transformation contained these desired second alterations.