A small 78 codon ORF, named HTL1 (Chen et al., unpublished results), situated between loci MAK31 and HSP30 on chromosome III of Saccharomyces cerevisiae, is required for growth at 37 degrees C. In this communication, we characterize the ORF and show that disruption of HTL1, besides preventing growth at 37 degrees C, causes genetic and/or epigenetic instability at 26 degrees C: ploidy increases in about 10% of cells grown from individual disruptants and a fraction of disruptant clones are predestined to a rapid and progressive loss of fertility during growth at 26 degrees C.