Stabilized pharmaceutical compositions comprising substantially monomeric interferon-beta (IFN-.beta.) and methods useful in their preparation are provided. The compositions comprise the IFN-.beta. solubilized in a low-ionic-strength formulation that maintains the composition at a pH of about 3.0 to about 5.0. Methods for preparing these compositions, and for increasing solubility of IFN-.beta. in pharmaceutical compositions, are provided.