In this study, we investigate the interaction between the tropical Intraseasonal Oscillation (ISO) and midlatitude atmospheric low-frequency variability, using observational data and numerical models, with a special emphasis on the role of the synoptic eddy feedback. A statistical closure for the synoptic eddy-to-low frequency flow feedback is constructed, based on a singular value decomposition (SVD) method with observational data. Applying this statistical closure to a barotropic model and a baroclinic 2½-layer model, we study the role of the synoptic eddy feedback in the midlatitude response to the tropical ISO forcing. Both observational and modeling studies show that the strongest synoptic eddy forcing appears at the Pacific and Atlantic storm-track regions, and the synoptic eddy exerts a positive feedback to the midlatitude low-frequency flow induced by tropical ISO forcing. Our numerical experiments demonstrate the possible role of midlatitude disturbance forcing in the ISO initiation at the equator. The signal of the midlatitude perturbations propagates southeastward in the form of a Rossby wave package. It may reach the equator within several days under either easterly or westerly basic flow regimes. The response at the equator has observed ISO-like structure and eastward propagation characteristics.