BACKGROUND AND OBJECTIVE. In this study, we attempted to determine whether the C/T polymorphism of the ET-1 gene was significantly associated with changes in several clinical characteristics after the 16-week combined exercise program in overweight middle-aged women. MATERIAL AND METHODS. The C/T polymorphism of the ET-1 gene was assayed using polymerase chain reaction, i.e., the TaqI restriction fragment length polymorphism method. RESULTS. The genetic variation in the ET-1 gene showed a significant association with the serum LDL cholesterol level as well as several parameters of physical fitness, including muscular endurance and power of the participants (P<0.05). In addition, this genetic variation showed a significant association with changes in muscular strength of the participants after the 16-week combined exercise program (P<0.05). CONCLUSIONS. Our data suggest that the C/T substitution on intron 4 of the ET-1 gene may be a useful genetic marker influencing muscular strength through a gene-exercise interaction and is associated with an interindividual difference of cardiovascular risk factors and parameters of physical fitness.