A digital computer program is described for the estimation of parameters in an open two compartment system distinguishing 3 models. The mathematical function to be fitted to a given set of experimental data is given initial estimates for the parameters of the function. The program uses an iterative procedure to adjust the parameters until the sum of squares of residuals has converged to a minimum. Assuming that a given substance is introduced into compartment 1, the function can be fitted to the set of experiment data of that compartment. A set of experimental data from compartment 2 can also be included in the minimizing function. Two optional weighting functions are presented. From the constants of the two-exponential functions the physiological parameters of the three models are determined. Experimental observations of compartment 1 only allow for calculation of physiological parameters of two of the models.