Cellular memory of past experiences has been observed in several organisms and across a variety of experiences, including bacteria "remembering" prior nutritional status and amoeba "learning" to anticipate future environmental conditions. Here, we show that Saccharomyces cerevisiae maintains a multifaceted memory of prior stress exposure. We previously demonstrated that yeast cells exposed to a mild dose of salt acquire subsequent tolerance to severe doses of H 2 O 2 . We set out to characterize the retention of acquired tolerance and in the process uncovered two distinct aspects of cellular memory. First, we found that H 2 O 2 resistance persisted for four to five generations after cells were removed from the prior salt treatment and was transmitted to daughter cells that never directly experienced the pretreatment. Maintenance of this memory did not require nascent protein synthesis after the initial salt pretreatment, but rather required long-lived cytosolic catalase Ctt1p that was synthesized during salt exposure and then distributed to daughter cells during subsequent cell divisions. In addition to and separable from the memory of H 2 O 2 resistance, these cells also displayed a faster gene-expression response to subsequent stress at .1000 genes, representing transcriptional memory. The faster gene-expression response requires the nuclear pore component Nup42p and serves an important function by facilitating faster reacquisition of H 2 O 2 tolerance after a second cycle of salt exposure. Memory of prior stress exposure likely provides a significant advantage to microbial populations living in ever-changing environments. N ATURAL environments are complex and often vary significantly in space and time, posing challenges for the organisms living within them. Single-cell organisms are particularly vulnerable, since variation in external conditions can directly impact internal homeostasis. Therefore, preparing for environmental change after early signs of fluctuation would present a significant advantage for cells growing in the wild. Indeed, many organisms can become tolerant to severe stress after an initial mild pretreatment with the same or a different stressor. This response, termed "acquired stress resistance," has been observed in microbes such as bacteria and yeast as well as in multicellular organisms including worms, plants, mammals, and even humans (Lu et al. 1993;Davies et al. 1995;Lewis et al. 1995;Lou and Yousef 1997;Swan and Watson 1999;Chi and Arneborg 2000;Schenk et al. 2000;Durrant and Dong 2004;Kandror et al. 2004;Scholz et al. 2005;Hecker et al. 2007;Kensler et al. 2007;Matsumoto et al. 2007). The conservation of this response suggests that it plays an important role in surviving environmental stress in diverse species.We previously conducted a systematic analysis of acquired stress resistance in Saccharomyces cerevisiae and found that the response is common, but not universal, for all pairs of stress treatments (Berry and Gasch 2008). The level and duration of mild-stress pretreatme...