Gene amplification is the mutation from one copy of a gene per genome to two or more copies of a gene per genome. Gene amplification is one type of mutation by which mammalian tumor cells become resistant to drugs used in chemotherapy. In addition, it has been reported that DNA damage increases amplification frequency in mammalian tumor cells. Several models of gene amplification have been proposed in the literature, and include those which cause errors in replication, errors in recombination, and those which cause chromosome breakage. Evidence exists for each of these models, but one mechanism is not favored over another. Our laboratory is studying the mechanisms involved in gene amplification in Saccharomyces cerevisiae. We have developed a system in yeast to detect co-amplifications of the ADH4 and CUP1 genes. We are using this system to identify the specific types of DNA damage that result in amplifications. Previous results from our laboratory showed that hydroxyurea, a DNA synthesis inhibitor, increased amplification rates in a normal yeast strain. Exposure of normal yeast cells to methyl methanesulfonate (MMS), which methylates DNA, or UV-irradiation, which causes pyrimidine dimers, showed an increase in amplification frequency. However, exposure to hydrogen peroxide, which causes single strand DNA breaks, or to *gamma*-rays, which cause single and double strand breaks, did not increase amplification frequency.