Experimental osmotic second virial cross coefficients are reported for linear and 8-arm star polystyrenes in three solvents: toluene, cyclohexane, and methylcyclohexane. The osmotic second virial cross coefficient for 8-arm star and linear polystyrene is always positive and within the osmotic second virial coefficients measured for the single polymers. The positive cross coefficient indicates net repulsion between the two different polymers in dilute solution. The extent of repulsion is greatest in toluene and least in cyclohexane. To relate the macroscopic second virial coefficient to microscopic interactions, the potential of mean force between linear and 6-arm star polymers was computed by molecular simulation. The interaction between nonbonded polymer segments is given by a square-well potential. Well width was set equal to one half of the segment diameter. Different solvent conditions were investigated by using different well depths. Potentials of mean force were then used to compute the osmotic second virial cross coefficients.