Oxygen isotopes in Carboniferous and Early Permian brachiopod shells from North America and the Russian Platform show up to 3 per mil variations suggestive of greenhouse-icehouse-greenhouse transitions. To evaluate the paleoclimatic significance of these temporal trends as well as interregional oxygen-isotope differences, we simulated Late Paleozoic climate (360, 320, and 280 Ma) utilizing the GENESIS v. 2.0 GCM. Paleogeographies are modified from Scotese et al. (1999, J. African Earth Sci. 28:99) with topographies inferred from tectonic relationships. The model was run with 1x and 4x modern preindustrial pCO₂ levels (280 ppm) for each time interval. During most of the Mississippian, the U.S. mid-continent (USM) was traversing the subtropical high of the Southern Hemisphere. By the mid-Carboniferous, the area had entered the ITCZ, and remained in the tropics through the Early Permian. Oxygen isotope data for brachiopod shells reflect in part this transit across climate zones. For the U.S. mid-continent, low oxygen isotopic values in the earliest Mississippian give way to high values in the mid-Mississippian. The d¹⁸O values decrease in the Late Mississippian, coinciding with the transition to wet, tropical climate. A d¹⁸O increase at or near the mid-Carboniferous boundary cannot be explained by precipitation-evaporation variations and is likely caused by decreasing temperatures and increasing ice volume. During the Permo-Carboniferous, the Russian Platform transited from the tropics to the subtropics. Rather than showing a d¹⁸O increase that might correspond to a progressive increase in salinity, the oxygen isotopic record shows variation on a roughly 20 m.y. time scale that likely reflects ice volume change. This includes a sharp Mid-Carboniferous d¹⁸O increase that coincides with the d¹⁸O increase in North America, further suggesting a transition from greenhouse to icehouse conditions. Oxygen isotope estimates of paleotemperature show good agreement with GCM results for some intervals (i.e., the earliest Pennsylvanian), but not for others (e.g., the latest Mississippian). Potential causes for this disagreement (e.g., inaccurate data or incorrect pCO₂ estimates) are being investigated. These results demonstrate the utility of coupling climate model and isotopic studies of Paleozoic climate.