In this paper, an actuator fault diagnosis scheme is proposed for a class of affine nonlinear systems with both known and unknown inputs. The scheme is based on a novel input/output relation derived from the considered nonlinear systems and the use of the recently developed high-order sliding-mode robust differentiators. The main advantages of the proposed approach are that it does not require a design of nonlinear observer and applies to systems not necessarily detectable. Conditions are provided to characterize the feasibility of fault detection and isolation using the proposed scheme and the maximum number of isolatable actuator faults. The efficacy of the proposed actuator fault diagnosis approach is tested through experiments on a laboratory 3D Crane, and the experimental results show that the proposed actuator fault diagnosis approach is promising and can achieve fault detection and isolation satisfactorily. (C) 2011 Elsevier Ltd. All rights reserved.