A novel parametric/non-parametric modeling paradigm was defined and used in characterization of synaptic transmission. In this paradigm, parametric and nonparametric techniques were incorporated in a complementary manner. Non-parametric method was used to generalize experimental data and extract system input/output properties. It provided a quantitative and intuitive way to validate a parametric model with respect to general, complete input patterns. Biological processes or mechanisms missed by the conventional parametric modeling approach were revealed and subsequently included into the modified parametric model.