1 A classic biogeographic pattern is the alignment of diploid, tetraploid and hexaploid races of creosote bush (Larrea tridentata) across the Chihuahuan, Sonoran and Mohave Deserts of western North America. We used statistically robust differences in guard cell size of modern plants and fossil leaves from packrat middens to map current and past distributions of these ploidy races since the Last Glacial Maximum (LGM). 2 Glacial/early Holocene (26-10 14C kyr BP or thousands of radiocarbon years before present) populations included diploids along the lower Rio Grande of west Texas, 650 km removed from sympatric diploids and tetraploids in the lower Colorado River Basin of south-eastern California/south-western Arizona. Diploids migrated slowly from lower Rio Grande refugia with expansion into the northern Chihuahuan Desert sites forestalled until after ???4.0 14C kyr BP. Tetraploids expanded from the lower Colorado River Basin into the northern limits of the Sonoran Desert in central Arizona by 6.4 14C kyr BP. Hexaploids appeared by 8.5 14C kyr BP in the lower Colorado River Basin, reaching their northernmost limits (???37??N) in the Mohave Desert between 5.6 and 3.9 14C kyr BP. 3 Modern diploid isolates may have resulted from both vicariant and dispersal events. In central Baja California and the lower Colorado River Basin, modern diploids probably originated from relict populations near glacial refugia. Founder events in the middle and late Holocene established diploid outposts on isolated limestone outcrops in areas of central and southern Arizona dominated by tetraploid populations. 4 Geographic alignment of the three ploidy races along the modern gradient of increasingly drier and hotter summers is clearly a postglacial phenomenon, but evolution of both higher ploidy races must have happened before the Holocene. The exact timing and mechanism of polyploidy evolution in creosote bush remains a matter of conjecture. ?? 2001 Blackwell Science Ltd.