This study examined the association between ACE I/D and ACTN3 R577X polymorphisms and muscle-related phenotypes and their adaptation to resistance training in older women. Volunteers (n=246;age=66.7 ± 5.5 years) underwent quadriceps strength assessment using isokinetics and fat-free mass by dual energy X-ray absorptiometry. 79 volunteers performed 24 weeks of resistance training and 75 were studied as controls. Genotypes were identified by standard procedures. No associations were observed for muscle strength for either gene, but volunteers carrying the D/D genotype presented higher appendicular fat-free mass compared to the I-allele carriers (6.3 ± 0.1 vs. 6.1 ± 0.1 kg/m (2)). The X-allele carriers presented higher relative fat-free mass when compared to homozygous R/R (16.3 ± 0.1 vs. 15.9 ± 0.1 kg/m (2)). All fat-free mass variables were significantly greater for carriers of both X/X and D/D genotypes. In response to RT, only the I-allele carriers significantly increased fat-free mass and a significant training × genotype interaction was noted. These findings do not support a pivotal role for the studied polymorphisms in determining muscle strength in older women, but suggest a modest role in fat-free mass determination. Of note, the results provide a novel insight that these genetic variations may interact to determine muscle mass in older women.