AbstractA statistical model is set forth that can be taken as a very general description of most data sets that arise from population pharmacokinetic studies. A (nontraditional) method for estimating the parameters of the model—called the NONMEM method in previously published papers—is described. This method involves a linearization of the model. An investigation of the effect of this linearization is reported. This investigation is an empirical one, based on the simulation of data from special cases of the model and the application of a few different estimation methods to these data. From the limited evidence in this investigation it appears that the linearization per se does not significantly adversely affect the estimates.