Germination and thermoinhibition in lettuce (Lactuca sativa 'Jianyexianfeng No. 1') seeds were investigated by a proteomic comparison among dry seeds, germinated seeds at 15°C, at 15°C after imbibition at 25°C for 48 h, or at 25°C in KNO 3 (all sampled individually at germination), and ungerminated seeds at 25°C, a thermoinhibitory temperature. Before twodimensional gel electrophoresis analysis, storage proteins (greater than 50% of total extractable protein) were removed by polyethylene glycol precipitation, which significantly improved the detection of less abundant proteins on two-dimensional gels. A total of 108 protein spots were identified to change more than 2-fold (P , 0.05) in abundance in at least one germination treatment. Nineteen proteins increasing and one protein decreasing in abundance during germination had higher abundance in germinated 15°C, 15°C after imbibition at 25°C for 48 h, and 25°C in KNO 3 seeds than in ungerminated 25°C seeds. Gene expression of 12 of those proteins correlated well with the protein accumulation. Methionine metabolism, ethylene production, lipid mobilization, cell elongation, and detoxification of aldehydes were revealed to be potentially related to lettuce seed germination and thermoinhibition. Accumulation of three proteins and expression of five genes participating in the mevalonate (MVA) pathway of isoprenoid biosynthesis correlated positively with seed germinability. Inhibition of this pathway by lovastatin delayed seed germination and increased the sensitivity of germination to abscisic acid. MVA pathway-derived products, cytokinins, partially reversed the lovastatin inhibition of germination and released seed thermoinhibition at 25°C. We conclude that the MVA pathway for isoprenoid biosynthesis is involved in lettuce seed germination and thermoinhibition.Seed germination is a complex process that is influenced by many environmental factors, such as light, temperature, and moisture (Bewley et al., 2013). Temperature is the most important environmental factor in regulating seed germination. For a given species, there is an optimal temperature or temperature range for seed germination, below and above which seed germination will be delayed or inhibited. The failure of a seed to germinate at supraoptimal temperatures is commonly called thermoinhibition (Reynolds and Thompson, 1971;Abeles, 1986). In nature, thermoinhibition of seed germination is an adaptive regeneration strategy for the seeds of winter annual plants, which prevents the seeds germinating during the summer when the conditions are not appropriate for seedling growth (Baskin and Baskin, 1998;Allen et al., 2007). However, thermoinhibition often creates a problem for crop production. It causes delayed and poor germination of crop species with low optimal temperatures for seed germination and thus limits the time and region for crop cultivation. In the case of lettuce (Lactuca sativa) seeds, which exhibit thermoinhibition at 25°C to 30°C depending on variety and production environment (Guzman et al., 1992...