Models describing complex processes often contain a large number of parameters as part of the nonlinear system. It is usually not possible in practice to identify all parameters because of the number and quality of measurement data as well as interactions among the parameters. A common approach is to select a set of parameters for estimation whereas other parameters are fixed at their nominal values. Such a parameter selection procedure is often based oil sensitivity analysis: however. the determined sensitivity values depend oil assumed values of the parameters and initial states. as well as known trajectories of the input signals. In this work parameter selection and experiment design procedures are integrated into a unified framework, which optimizes a criterion of the Fisher information matrix and simultaneously takes the effect of uncertainty in the parameter values into account. A hybrid method combining a genetic algorithm and a simultaneous perturbation stochastic approximation is developed to solve the resulting mixed-integer nonlinear programming problem. The technique is illustrated oil a model of a continuously-stirred tank reactor and of a signal transduction pathway. (C) 2008 American Institute of Chemical Engineers.