It is relatively easy to represent by computer simulation the observed Rayleigh equilibrium fringe data for systems that are both associative and nonideal in the thermodynamic sense, and to extract the determinant parameters (see, for example, Roark, D., and D. A. Yphantis, 1969, Ann. NY Acad. Sci., 164:245-278; and Johnson M. L., J. J. Correia, D. A. Yphantis, and H. R. Halvorson, 1981, Biophys. J., 36:575-588). It is, however, considerably more difficult to represent systems that are both polydisperse (namely, those that consist of noninteracting species of different molecular weight) and nonideal, although the ideal case has been well described (see, for example, Tindall, S. H., and K. C. Aune, 1982, Anal. Biochem. 120:71-84). Here we show that the representation of nonideal polydisperse systems is now possible, after certain assumptions, by using a two-part interdependent minimization routine that uses readily available numerical packages. The method is applied to a well-characterized mucus glycoprotein (Mr approximately 2 X 10(6)) from the bronchial secretion of a cystic fibrosis patient. An excellent fit to the observed fringe data is obtained for a polydisperse three-component system, with a value for the second virial coefficient, B, of 0.57 ml mol g-2.