The binary blend lattice cluster theory (LCT) is applied to isotopic polystyrene (PSD/PSH) blends to study the combined influence on blend physical properties of local correlations, monomer molecular structure, and blend compressibility, as well as of asymmetries in interactions, molecular weights, and monomer structures. The LCT computations of the small-angle neutron scattering effective interaction parameter chi(eff), the coexistence curve, and the interfacial profile in phase-separated PSD/PSH blends provide good agreement with experimental data, indicating internal consistency. The computations do not yield the parabolic upward composition dependence of chi(eff) that is observed for isotopic blends of polybutadienes and polyethylenes. We speculate that this upward behavior arises from the random copolymer nature of these systems.