Prior data in young individuals suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism interacts with exercise to affect athletic performance, but the direction of the genotype effect depends on the outcome assessed (endurance vs. strength). The purpose of this study was to determine whether the ACE I/D genotype influences physical function responses to exercise training in older individuals. Physical function (muscle strength, walking distance, and self-reported disability) was measured before and after an 18-month randomized, controlled exercise trial in 213 older (>or= 60 yrs), obese (BMI >or= 28 kg/m2) men and women. Exercise training consisted of walking and light weight lifting for one hour 3 times/wk. At baseline, there were no associations between ACE I/D genotype and measures of physical function. Following exercise training, individuals with the DD genotype showed greater gains in knee extensor strength compared to II individuals. There was a significant (p = 0.014) interaction between ACE I/D genotype and exercise treatment on percent change in knee strength. In addition, there was a trend towards a greater improvement in physical disability score in DD genotypes (p = 0.13), but changes in 6-minute walk distance were not different between genotype groups. Thus, changes in muscle strength with exercise training in older individuals may be dependent on ACE I/D genotype.