A method, system, and computer program product for automated and semi-automated measurements of pleural space and/or pleural thickening in thoracic CT images to identify the presence and quantify the extent of pleura-based disease, including obtaining a CT image including the pleural space and/or the pleural thickening, segmenting lungs in the obtained image, obtaining an initial endpoint on a chest wall or a mediastinum boundary; determining a terminal endpoint on a boundary of the at least one segmented lung; and determining a distance between said initial endpoint and said the terminal endpoint as the extent of the pleural space and/or the pleural thickening. Exemplary embodiments include determining the extent of pleural space and/or pleural thickening based on linear distance, area, and volume of the space between the lung boundary and at least one of the chest wall and the mediastinum boundary. These pleural determinations may be used to quantify the extent of disease in a particular case as additional information to be incorporated into a radiologist's decision-making process, or as part of a computer-aided diagnostic scheme that alerts radiologists of the potential for pleural disease in the case.