Blood supply is critical to fuel muscle contraction and limits exercise performance. The presence of a silencer sequence in intron 16 (insertion, I) in the ACE (angiotensin converting enzyme) gene, which is the enzyme that converts the vasoconstrictor angiotensin (Ang) into its active form Ang2, has been associated with enhanced endurance capacity (Montgomery et al. 1998 and Scanavini et al. 2002). However, conflicting evidence exists on the association of ACE genotypes with regard to the presence (or absence) of the I sequence and human performance (Rankinen et al. 2000, Amir et al. 2007 and Zhao et al. 2003). Adaptations of capillary supply lines in muscle contribute and explain the altered endurance phenotype in ACE genotypes, with an ACE insertion sequence, due to reduced ACE gene expression in muscle. Participants were untrained healthy medical students (n=12) recruited from the University of Berne. Aerobic performance was measured and muscle biopsies collected, under a local anaesthetic (lidocaine), from the Vastus lateralis muscle. Ultra-structure and gene expression were quantified in biopsies with morphometry and cDNA microarrays. DNA was extracted and the ACE genotype identified post-hoc with specific primers. The participants fell into two categories: DD and ID. The DD genotype vs. the ID genotype demonstrated increased mRNA expression of ACE and Ang2 receptors, elevated mitochondrial density, capillary density, and reduced fiber size (see fig. 1). Maximal oxygen uptake during bicycle exercise in the DD genotype was elevated by 27% and correlated positively and negatively, respectively, with mitochondrial volume density (r=0.65) and fibre area (r=-0.53) in the investigated knee extensor muscle. The investigated, not-specifically trained population demonstrated a shift towards a muscle phenotype with improved substrate supply and aerobic metabolism. This suggests that expressional alterations in the local Ang2 signalling system intervene in the manifestation of an endurance phenotype via the modulation of capillarity and aerobic capacity in locomotor muscle.