The R577X polymorphism in the -actinin-3 encoding gene (ACTN3) has been associated with elite athletic performance, and recently with differences in isometric and dynamic muscle strength and power in the general population. PURPOSE: We sought to determine the association of ACTN3 R577X genotype with muscle strength and mass phenotypes in men and women across the adult age span. METHODS: Eight hundred forty-eight (n=848) adult volunteers (454 men and 394 women) aged 22-90 years were genotyped for ACTN3 R577X. Knee extensor (KE) shortening and lengthening peak torque values were determined using isokinetic dynamometry and fat free mass (FFM) by dual-energy X-ray absorptiometry. RESULTS: Women deficient in -actinin-3 (X/X; n=53) displayed lower KE shortening peak torque (30°/sec: 89.5 ± 3.5 vs. 99.3 ± 1.4 N•m, p=0.011; 180°/sec: 60.3 ± 2.6 vs. 67.0 ± 1.0 N•m, p=0.019) and KE lengthening peak torque (30°/sec: 122.8 ± 5.7 vs. 137.0 ± 2.2 N•m, p=0.022; 180°/sec: 121.8 ± 5.8 vs. 138.5 ± 2.2 N•m, p=0.008) compared to R/X+R/R women (n=341). Women X/X homozygotes also displayed lower levels of both total body FFM (38.9 ± 0.5 vs. 40.1 ± 0.2 kg, p=0.040) and lower limb FFM (11.9 ± 0.2 vs. 12.5 ± 0.1 kg, p=0.044) compared to R/X+R/R women. No genotype-related differences were observed in men. CONCLUSION: Our results indicate that the absence of -actinin-3 protein (i.e., ACTN3 X/X genotype) influences KE peak torque and FFM in women but not men.