Nearest-neighbor recognition measurements have been made using exchangeable mimics of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in the liquid-ordered (l(o)) and liquid-disordered (l(d)) states. In the l(d) phase, the net interaction between these two lipids is repulsive. In the l(o) phase, their interactions are neither attractive nor repulsive. These results, together with previous nearest-neighbor measurements, imply that the overall driving force for lipid domain formation in bilayers composed of high-melting lipids, low-melting lipids, and cholesterol, corresponds to a strong pull (attraction) between the high-melting lipids and cholesterol, a significant push (repulsion) between the low-melting and high-melting lipids, and a significant push between the low-melting lipids and cholesterol. In a broader context, these results provide strong support for the notion that repulsive forces play a major role in the formation of lipid rafts.