INTRODUCTION: Quadriceps dysfunction is important in chronic obstructive pulmonary disease (COPD), with an associated increased proportion of type II fibers. Investigation of protein synthesis and degradation has yielded conflicting results, possibly due to study of whole biopsy samples, whereas signalling may be fiber-specific. Our objective was to develop a method for fiber-specific gene expression analysis. METHODS: 12 COPD and 6 healthy subjects underwent quadriceps biopsy. Cryosections were immunostained for type II fibers, which were separated using laser capture microdissection (LCM). Whole muscle and different fiber populations were subject to quantitative polymerase chain reaction (qPCR). RESULTS: Muscle-RING-finger-protein-1(MURF-1) and Atrogin-1 were lower in type II fibers of COPD versus healthy subjects (P=0.02 and P=0.03, respectively), but differences were not apparent in whole muscle or type I fibers. DISCUSSION: We describe a novel method for studying fiber-specific gene expression in optimum-cutting-temperature (OCT) compound-embedded muscle specimens. LCM offers a more sensitive way to identify molecular changes in COPD muscle. This article is protected by copyright. All rights reserved.