Fault detection and diagnosis is a critical approach to ensure safe and efficient operation of manufacturing and chemical processing plants. Although multivariate statistical process monitoring has received considerable attention, investigation into the diagnosis of the source or cause of the detected process fault has been relatively limited. This is partially due to the difficulty in isolating multiple variables, which jointly contribute to the occurrence of fault, through conventional contribution analysis. In this work, a method based on probabilistic principal component analysis is proposed for fault isolation. Furthermore, a branch and bound method is developed to handle the combinatorial nature of problem involving finding the contributing variables, which are most likely to be responsible for the occurrence of fault. The efficiency of the method proposed is shown through benchmark examples, such as Tennessee Eastman process, and randomly generated cases. (C) 2010 Elsevier Ltd. All rights reserved.