The genetic factors determining the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with adaptation to exercise training in a cross between FVB/NJ (FVB) and C57BL/6J (B6) mice. Mice completed an exercise performance test before and after a 4-week treadmill running program, and changes in exercise capacity, expressed as work (kg·m), were calculated. Changes in work in F2 mice averaged 1.51 ± 0.08 kg·m (94.3 ± 7.3%) with a range of -1.67 to +4.55 kg·m. All F₂ mice (n = 188) were genotyped at 20 cM intervals using 103 SNPs and genome-wide linkage scans were performed for pre-training, post-training, and changes in work. Significant QTL for pre-training work were located on chromosomes 14 at 4.0 cM (3.72 LOD), and 19 at 34.4 cM (3.63 LOD). For post-training work significant QTL were located on chromosomes 3 at 60 cM (4.66 LOD) and 14 at 26 cM (4.99 LOD). Suggestive QTL for changes in work were found on chromosomes 11 at 44.6 cM (2.30 LOD) and 14 at 36 cM (2.25 LOD). When pre-training work was used as a covariate, a potential QTL for the change in work was identified on chromosome 6 at 68 cM (3.56 LOD). These data indicate that one or more QTL determine exercise capacity and training responses in mice. Furthermore, these data suggest that the genes that determine pre-training work and training responses may differ.