This work deals with a new hybrid approach for the detection and diagnosis of faults in different parts of fed-batch and batch reactors. In this paper, the fault detection method is based on the using of Extended Kalman Filter (EKF) and statistical test. The EKF is used to estimate on-line in added to the state of reactor the overall heat transfer coefficient (U). The diagnosis method is based on a probabilistic neural network classifier. The Inputs of the probabilistic classifier are the input-output measurements of reactor and the parameter U estimated by EKF, while the outputs of the classifier are fault types in reactor. This new approach is illustrated for simulated as well as experimental data sets using two cases of reactions: the first is the oxidation of sodium thiosulfate by hydrogen peroxide and the second is alkaline hydrolyse of ethyl benzoate in homogeneous hydro-alcoholic. Finally, the combination of the estimated parameter U using EKF and probabilistic neural network classifier provided the best results. These results show the performance of the proposed approach to monitoring the semi-batch and batch reactors. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.