Recently, some authors have hypothesized that the "optimum" polygenic profile differs between power and endurance-oriented athletes due to the different phenotype traits that determine performance in both type of events. The results on the association between polymorphism and elite athletic performance are controversy. Despite some studies having found a positive association between genetic marker and athletic performance, other studies reported negative results. PURPOSE: The aim of the present study was to investigate the association between the ACTN3, ACE and BK2 genotypes and elite sport performance in Italians soccer players. METHODS: The males sample analyzed in this study was composed by 45 top-level soccer players (S) from Italy and 53 Italians control group (C). Chi-square test was used to assess the difference genotype distributions of ACTN3 and ACE and BK2 between groups. Relationships were evaluated by forward stepwise multiple regression analysis with the Squat Jump (SJ) as dependent variable and competition level (first and second division), ACTN-3, ACE and BK2 genotypes as independent variables. RESULTS: For ACE, the DD genotype and D allele were found to be at very high frequency in all soccer players and control cohorts (DD, D: S = 53.3%, 71.1%; C= 50.9%, 68.8%). Athletes did not significantly differ from controls in ACE genotype distribution (χ2 = 0.507, df = 2, p = 0.775). Chi-square test showed no significant difference between groups for ACTN-3 (χ2=0.570, df = 2, p = 0.751) and BK2 (χ2=0.257, df = 2, p = 0.879) genotype distributions. Forward stepwise multiple regression analysis suggest a significant relationship between SJ and competition level (R2=0.2197, F=9.011, df=1, p=0.005), and ACE (R2=0.1013, F=4.628, df=2, p=0.039), and ACTN-3 (R2=0.0852, F=4.309, df=3, p=0.046). The athletes with DD and RR genotypes belong to the first division and they showed a greater muscle strength performance respect to those with different genotypes (DD,ID,II: 41 cm, 40 cm, 37 cm; RR,RX,XX: 42 cm, 39 cm, 39 cm). The multivariate model combining genotypic data and competition level significantly predicted muscle strength performance in soccer players (model F=6.8453, df=3, p=0.001), and variance explained by the function was 34.69%. CONCLUSION: We observed that there might be an interaction of two polymorphisms (ACE and ACTN-3) able to discriminate the potential of becoming a top-level soccer competitor, yet the contribution of genetic factors (at least of those we studied) to sports performance was relatively low. Research Project financed by RAS, L.R. n.17/99 art.40 and Master and Back Programme 2008.