We describe a new method for probing phase separation of polymer-blend systems in spherical microparticles generated from microdroplets of dilute polymer solution. Two-dimensional optical diffraction-a technique sensitive to material inhomogeneity on a length scale of approximate to 30 nm-is used to probe phase-separation behavior of bulk-immiscible polymers in attoliter and femtoliter volumes. Under conditions of rapid solvent evaporation (approximate to 2-10 ms) and relatively low polymer mobility, homogeneous composite particles can be formed using different polymers that ordinarily undergo phase separation in bulk preparations. We show that, for homogeneous particles, the refractive index (related to material dielectric constant) can be tuned by adjusting the relative weight, fractions of polymers in the blend. Molecular dynamics simulations of polymer-blend microparticles are presented to illustrate at a molecular level effects of polymer interactions and boundary conditions on phase separation in polymer-blend nanoparticles. Finally, we show that polymer mobility affects phase-separation behavior in microparticles using mixtures of poly(vinyl alcohol)s with low molecular weight (high-mobility) poly(ethylene glycol) oligomers. For higher molecular weight polymers (>10 K), surface energy constraints inhibit phase separation, and the polymer-blend particles are observed to be homogeneous to within experimental resolution. Conversely, blends of low molecular weight PEG with PVA phase-separate on a time scale of several minutes to form heterogeneous composite particles.