alpha-Actinin-3 is a Z-disc structural protein found only in type II muscle fibers. The X allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and alpha-actinin-3 deficiency in XX homozygotes. Associations between the R577X polymorphism and the muscle-power performance of elite athletes have been described earlier. About 45% of the fiber type proportions are determined by genetic factors. The ACTN3 variant could be one of the contributing genes in the heritability of fiber type distribution through its interaction with calcineurin. The aim of this study was to quantify the association between the polymorphism and muscle fiber type distribution and fast-velocity knee extension strength. Ninety healthy young men (18-29 y) were genotyped for ACTN3 R577X. Knee extensor strength was measured isometrically (45 degrees ) and at different dynamic velocities (100-300 degrees /s) on a programmable dynamometer. Twenty-two XX and twenty-two RR subjects underwent a biopsy of the right vastus lateralis muscle. Fiber type composition was determined by immunohistochemistry. Homozygotes for the R allele show significantly higher relative dynamic quadriceps torques at 300 degrees /s, compared with XX carriers (P < 0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers were greater in the RR than the XX genotype group (P < 0.05), and alpha-actinin-3 protein content is systematically higher in type IIx compared with type IIa fibers (staining intensity ratio IIx to IIa = 1.17). This study shows that the mechanism, by which the ACTN3 polymorphism has its effect on muscle power, might rely on a control function of fiber type proportions.