A computer program for non-linear least squares minimization has been applied to construct temperature-composition phase diagrams for several binary systems of different phospholipids based on their calorimetric data. The calculated phase diagram is guided to fit the calorimetric data with two adjustable parameters that describe the non-ideal mixing of lipid components in the gel and liquid-crystalline phases. The parameter estimation procedure is presented to show that the computer program can be used not only to generate phase diagrams with characteristic shapes but also to numerically estimate the lipid-lipid pair interactions between the mixed and the like pairs in the two-dimensional plane of the bilayer in both the gel and liquid-crystalline states. The binary lipid systems examined include dimyristoylphosphatidylcholine/1-palmitoyl-2-stearoylphosphatidylchol ine, 1-capryl-2-behenoylphosphatidylcholine/1-behenoyl-2-lauro ylphosphatidylcholine, and 1-stearoyl-2-caprylphosphatidylcholine/dimyristoylphosphatidylchol ine.