When the isthmian land bridge triggered the Great American Interchange, a large majority of land-mammal families crossed reciprocally between North and South America at about 2.5 Ma (i.e., Late Pliocene). Initially land-mammal dynamics proceeded as predicted by equilibrium theory, with roughly equal reciprocal mingling on both continents. Also as predicted, the impact of the interchange faded in North America after about 1 m.y. In South America, contrary to such predictions, the interchange became decidedly unbalanced: during the Pleistocene, groups of North American origin continued to diversify at exponential rates. Whereas only about 10% of North American genera are derived from southern immigrants, more than half of the modern mammalian fauna of South America, measured at the generic level, stems from northern immigrants. In addition, extinctions more severely decimated interchange taxa in North America, where six families were lost, than in South America, where only two immigrant families became extinct.This paper presents a two-phase ecogeographic model to explain the asymmetrical results of the land-mammal interchange. During the humid interglacial phase, the tropics were dominated by rain forests, and the principal biotic movement was from Amazonia to Central America and southern Mexico. During the more arid glacial phase, savanna habitats extended broadly right through tropical latitudes. Because the source area in the temperate north was six times as large as that in the south, immigrants from the north outnumbered those from the south. One prediction of this hypothesis is that immigrants from the north generally should reach higher latitudes in South America than the opposing contingent of land-mammal taxa in North America. Another prediction is that successful interchange families from the north should experience much of their phylogenetic diversification in low latitudes of North America before the interchange. Insofar as these predictions can be tested, they appear to be upheld.