Susceptibility to scrapie is largely controlled by the PRNP gene in mice and in several other species. However, individuals with identical scrapie susceptibility Prnp alleles may have very different incubation periods, suggesting the influence of other environmental and genetic factors. To detect loci influencing susceptibility to TSE, two mouse lines carrying the same PRNP genotype (C57BL and RIII) were crossed to produce an F2 population inoculated intracerebrally with a mouse-adapted scrapie strain. Linkage was studied between 72 markers and the age of death of F2 animals. Six QTL were detected, two at a genome-wide significant level (chromosomes 5 and 7) and four at a genome-wide suggestive level (chromosomes 4, 6, 8, and 17). Our results confirmed the existence of some QTL that were detected previously (chromosomes 4, 6, 7, and 8) while others were found only in the present study (chromosomes 5 and 17). Furthermore, it seems that some QTL (chromosomes 4 and 8) are involved in resistance to scrapie as well as to BSE.