Ume6p is a nonessential transcription factor that represses meiotic gene expression during vegetative growth in budding yeast. To relieve this repression, Ume6p is destroyed as cells enter meiosis and is not resynthesized until spore wall assembly. The present study reveals that spores derived from a ume6 null homozygous diploid fail to germinate. In addition, mutant spores from a UME6/ume6 heterozygote exhibited reduced germination efficiency compared with their wild-type sister spores. Analysis of ume6 spore colonies that did germinate revealed that the majority of cells in microcolonies following the first few cell divisions were inviable. As the colony developed, the viability percentage increased and achieved wild-type levels within approximately six cell divisions, indicating that the requirement for Ume6p in cell viability is transient. This function is specific for germinating spores as Ume6p has no or only a modest impact on the return to the growth ability of cells arrested at other points in the cell cycle. These results define a new role for Ume6p in spore germination and the first few subsequent mitotic cell divisions.