Seed thermoinhibition (inhibition of germination at warm temperatures) can reduce seedling emergence and stand establishment of cultivated lettuce (Lactuca sativa L.) when soil temperatures are warm (>25°C) at planting. Genetic variation for high temperature germination tolerance exists among accessions of lettuce and related wild species. Seeds of a L. serriola accession (UC96US23) germinated 100% up to 37°C, while seeds of L. sativa 'Salinas' were completely inhibited from germinating at temperatures above 31°C. A recombinant inbred line population, developed from a cross between 'Salinas' and UC96US23, was analyzed for germination capacity at high temperatures. A major quantitative trait loci (QTL) for high temperature germination (Htg6.1) and additional QTL having smaller effects were identified. Near-isogenic lines confirmed the effect of Htg6.1 and are being utilized for further fine-mapping of the locus. Candidate genes associated with seed dormancy have been mapped to test for co-localization with thermoinhibition QTL. Expression patterns of candidate genes, particularly those associated with gibberellin and abscisic acid synthesis and metabolism, have also been analyzed in relation to genotype and germination temperature. Combined genetic and molecular analyses hold promise for elucidating the physiological regulation of thermoinhibition and for developing lettuce cultivars with enhanced stand establishment of warm temperature plantings.