Recent reports suggest that a polymorphism of the alpha-actinin-3 gene (ACTN3) is associated with muscle power. Homozygosity for the R577X single nucleotide polymorphism (SNP) at the ACTN-3 gene locus results in the absence of ACTN-3 expression. To examine the influence of this polymorphism on baseline peak power (PP) and PP changes with strength training (ST), we studied 53 older men (64 (9) yr) and 65 older women (65 (9) yr) before and after a 10-week single leg knee extension strength training (ST) program. At baseline, when men and women were combined, the XX group had a relative PP (tested at 70% of 1 RM) that was 36 ± 17 watts (W) higher than the RR group (279 ± 12 W, P < 0.05), and the RX group was 43 ± 17 W higher than the RR group (P < 0.05), when age and sex differences were used as covariates. As a result of the ST program, change in absolute PP in the RR group was significantly higher than in the XX group (48 ± 7 W vs. 26 ± 7 W, P < 0.05), when the data were adjusted for age, sex, and changes in the untrained leg. Separate analyses by sex found that in women the XX group had a significantly higher baseline absolute PP than the RR (240 ± 11 W vs. 208 ± 9 W) and RX groups (240 ± 11 W vs. 208 ± 10 W, both P < 0.05), when age and baseline fat-free mass were covaried. The change in absolute PP in the RR group was significantly higher than in the XX group (63 ± 14 W vs. 25 ± 9 W, P < 0.05) with ST in men, when the data were adjusted for age and changes in the untrained leg. There were no differences among genotype groups in women for change in absolute PP. These results suggest that the ACTN3 R577X polymorphism may influence peak power at baseline and in response to ST in older adults, but this relationship is strongly dependent on the sex of the group studied.