Introduction Skeletal muscle impairment is an important feature of chronic obstructive pulmonary disease (COPD). Renin-angiotensin system activity influences muscle phenotype, so we wished to investigate whether it affects the response to pulmonary rehabilitation. Methods Two studies are described; in the first, the response of 168 COPD patients (mean FEV1 51.9%predicted) to pulmonary rehabilitation was compared between different ACE Insertion/Deletion polymorphism genotypes. In a second, independent COPD cohort (n=373), baseline characteristics and response to pulmonary rehabilitation were compared between COPD patients who were or were not taking angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor antagonists (ARB). Results In study 1, the incremental shuttle walk distance improved to a similar extent in all three genotypes; DD/ID/II (n=48/91/29) 69(67)m, 61(76)m, 78(78)m respectively (p>0.05). In the second study, fat free mass index was higher in those on ACE-I/ARB (n=130) than those who were not (n=243) 17.8(16.0, 19.8)kgm-2 vs 16.5(14.9,18.4) kgm-2 (p