Controlling non-affine non-linear systems is a challenging problem in control theory. In this paper, we consider adaptive neural control of a completely non-affine pure-feedback system using radial basis function (RBF) neural networks (NN). An ISS-modular approach is presented by combining adaptive neural design with the backstepping method, input-to-state stability (ISS) analysis and the small-gain theorem. The difficulty in controlling the non-affine pure-feedback system is overcome by achieving the so-called "ISS-modularity" of the controller-estimator. Specifically, a neural controller is designed to achieve ISS for the state error subsystem with respect to the neural weight estimation errors, and a neural weight estimator is designed to achieve ISS for the weight estimation subsystem with respect to the system state errors. The stability of the entire closed-loop system is guaranteed by the small-gain theorem. The ISS-modular approach provides an effective way for controlling non-affine non-linear systems. Simulation studies are included to demonstrate the effectiveness of the proposed approach. (c) 2006 Elsevier Ltd. All rights reserved.