We isolated a Saccharomyces cerevisiae mutant, CH108, which shows hypersensitivity to cycloheximide, bleomycin, actinomycin D, 5-fluorouracil, and several other antibiotics. The mutant cells showed irregular shapes with swelling and were also hypersensitive to Zymolyase digestion. The mutant cell wall was swelled and twice as thick as the wild type cell wall. These defects were completely reversed by introduction of a genomic clone on a single-copy vector. Restriction analysis and sequencing showed that the responsible gene, DHS1, encodes a novel hydrophilic polypeptide of 483 amino acids.