This paper proposes a novel subspace approach towards identification of optimal residual models for process fault detection and isolation (PFDI) in a multivariate continuous-time system. We formulate the problem in terms of the state space model of the continuous-time system. The motivation for such a formulation is that the fault gain matrix, which links the process faults to the state variables of the system under consideration, is always available no matter how the faults vary with time. However, in the discrete-time state space model, the fault gain matrix is only available when the faults follow some known function of time within each sampling interval. To isolate faults, the fault gain matrix is essential. We develop subspace algorithms in the continuous-time domain to directly identify the residual models from sampled noisy data without separate identification of the system matrices. Furthermore, the proposed approach can also be extended towards the identification of the system matrices if they are needed. The newly proposed approach is applied to a simulated four-tank system, where a small leak from any tank is successfully detected and isolated. To make a comparison, we also apply the discrete time residual models to the tank system for detection and isolation of leaks. It is demonstrated that the continuous-time PFDI approach is practical and has better performance than the discrete-time PFDI approach. (C) 2003 Elsevier Science Ltd. All rights reserved.