Several genome-wide linkage scans have been carried out to identify quantitative trait loci for type 2 diabetes and related metabolic phenotypes. However, no previous linkage scans have focused on the response to exercise training of relevant metabolic traits. We performed a genome-wide linkage scan for baseline fasting glucose, insulin, and C-peptide and their responses to a 20-week exercise training program in nondiabetic white and black men and women from the HERITAGE Family Study. In SIBPAL linkage analyses, the maximum number of sibpairs available was 344 and 93 for baseline phenotypes and 300 and 72 for exercise training response phenotypes in whites and blacks, respectively. A total of 509 markers with an average spacing of 6.0 Mb were used. The strongest linkage was found for the changes in fasting insulin in response to exercise training with a marker in the leptin gene on 7q31 (empirical multipoint P = 0.0004) in whites. In blacks, the strongest linkage was observed for baseline fasting glucose on 12q13-q14 (empirical multipoint P = 0.0006). These regions harbor several potential candidate genes. The present findings may be important in identifying individuals at increased risk of developing type 2 diabetes and who are most likely to benefit from a physically active lifestyle.