Surgical and bronchoscopic lung volume reduction (LVR) have been demonstrated to improve lung function, dyspnea and quality of life in patients with severe pulmonary emphysema. The most important functional prerequisite for a successful LVR is hyperinflation measured by body plethysmography. A residual volume (RV) of more than 180% predicted and a RV/total lung capacity (TLC) ratio of more than 0.58 were inclusion criteria in major LVR trials. Here we report a successful LVR in a 68-year-old man with advanced, heterogeneous emphysema without plethysmographic evidence of severe hyperinflation (RV/TLC 0.45). Computed tomography (CT) revealed severe, partly bullous upper lobe emphysema and subtle fibrotic changes with volume loss of lower lobes. Since lower lobes appeared compressed by upper lobe emphysema, these target areas were removed by thoracoscopic LVR. Four months later, the patient reported major improvements of dyspnea, FEV (by 1.27 L) and 6-minute walking distance (by 150 meters). LVR reduced total lung volume measured by CT-volumetry by 0.5 L and upper lobe volume by 1.85 L while lower lobe volume increased by +1.34 L. Low density volume (-950 HU) reflecting emphysema was reduced by 1.73 L. We conclude that the opposing effects of emphysema and fibrosis resulted in a barely increase in total lung volume that was only slightly reduced by LVR. Nevertheless, resection of emphysematous target areas identified by quantitative CT analysis provided major clinical and physiologic improvements related to decompression of low-compliance lower lobe areas retracted by early fibrosis. Therefore, in the combined presence of severe, heterogeneously distributed emphysema and fibrosis, LVR may improve respiratory mechanics even if RV/TLC, an established body-plethysmographic predictor of LVR success is not severely elevated.