The allometric scaling of metabolic rate with organism body mass can be partially accounted for by differences in cellular metabolic rates. For example, hepatocytes isolated from horses consume almost ten-fold less oxygen per unit time as mouse hepatocytes [Porter and Brand, 1995. Am J Physiol. 269:R226-228]. This could reflect a genetically programmed, species specific, intrinsic metabolic rate setpoint, or simply the adaptation of individual cells to their particular in situ environment (i.e. within the organism). We studied cultured cell lines derived from ten mammalian species, with donor body masses ranging from 5-600,000 g to determine whether cells propagated in an identical environment (media) exhibited metabolic rate scaling. Neither metabolic rate, nor the maximal activities of key enzymes of oxidative or anaerobic metabolism scaled significantly with donor body mass in cultured cells, indicating the absence of intrinsic, species-specific, cellular metabolic rate setpoints. Furthermore, we suggest that changes in the metabolic rates of isolated cells probably occur within 24 hrs and involve a reduction of cellular metabolism towards values observed in lower metabolic rate organisms. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms. To examine the effect of oxygen on steady-state cellular respiration rates, we grew cells under a variety of physiologically relevant oxygen regimes. Long-term exposure to higher medium oxygen levels increased respiration rates of all cells, consistent with the hypothesis that higher rates of oxygen delivery in smaller mammals might increase cellular metabolic rates.