Uncertainties about the origin of the many disequilibrium or 'vital effects' in a variety of calcifying organisms, and whether these effects are constant or variable, have hampered paleoceanographic application of carbon and oxygen isotopic ratios. Unraveling the source of these effects will improve paleoceanographic applications and may provide new information on changes in cell physiology and ecology. Culture of eight species of coccolithophorids, a dominant marine phytoplankton group, reveals a 5‰ array of disequilibrium or 'vital effects' in both the carbon and oxygen isotopic composition of coccolith calcite. In moderate light and nutrient-replete cultures, oxygen isotopic fractionation and carbon isotopic fractionation correlates directly with cell division rates and correlates inversely with cell size across a range of species. However, when growth rates of a single species are increased or decreased by higher or lower light levels, ε18O is relatively invariant. Likewise, growth rate variations as a function of temperature do not influence coccolith ε18O; the slope of the ε18O vs. temperature relation in cultures of both Gephyrocapsa oceanica and Helicosphaera carteri is the same as for abiogenic carbonates. This suggests a constant, species-specific isotopic fractionation which does not vary with cell physiology. The constancy of vital effects suggests that coccolith stable isotopes will provide reliable phase for paleoceanographic reconstruction of temperature and seawater chemistry, as long as monospecific fractions are analyzed or changes in nannofossil assemblages are accounted for with species-specific correction factors. We suspect that the cell size, and its constraints on the rate of CO2 diffusion relative to C fixation, may be the first order influence on coccolith stable isotope vital effects. A quantitative model of this process may provide important constraints on mechanisms of carbon acquisition of coccolithophorids in both modern and extinct species. © 2003 Elsevier Science B.V. All rights reserved.