The oxygen isotope composition of both calcite and aragonite of the pelecypod Inoceramus is lighter than the composition of the aragonite of associated baculites and other cephalopods from the western interior region, the Gulf and Atlantic Coastal Plains, parts of Canada, and West Greenland. This difference cannot be explained by biotic and oceanographic factors or by postdepositional alteration of original isotopic compositions. Metabolic fractionation of oxygen isotopes by Inoceramus is strongly implied by the data and is not contradicted by what is known of the processes involved in the biologic deposition of shell carbonate. In addition, the oxygen isotope compositions of the inocerams and of some baculites are so light as to indicate temperatures greater than 30° C, which is too high for mollusks to tolerate. The unreasonable range of the indicated temperatures seems to be partly the result of metabolic fractionation of oxygen and partly the result of the Late Cretaceous sea in the western interior region having had a light oxygen isotope composition because of dilution with fresh water. The carbon isotope composition of the aragonite from Inoceramus is consistently heavier than that of the calcite in the same specimen by amounts ranging from 1 to 3 per mil. Metabolic fractionation of carbon isotopes within Inoceramus thus is indicated. The carbon isotope composition of the aragonite from baculites and other cephalopods is consistently lighter than that in either the aragonite or calcite in Inoceramus, indicating either that the cephalopods fractionated carbon isotopes from the dissolved carbonate in sea water differently than did inocerams or that the cephalopods utilized carbon of a different isotopic composition, probably from their food source, for their metabolic processes. While oxygen isotope data from the inocerams are not useful for paleotemperature interpretations, the oxygen isotope data from the baculites, if taken at face value, suggest either warmer temperatures for the western interior sea than around the periphery of Cretaceous North America, or water of oxygen isotope composition lighter than world oceans, or both. Data from British Columbia, southeastern Alaska, and West Greenland to the Gulf Coastal Plain do not indicate a well-developed latitudinal distribution of temperature in Late Cretaceous time. A general decline in temperatures during late Campanian and early Maestrichtian time is not evident. © 1969, The Geological Society of America, Inc.