The thermal dependence (0–40°C) of Na+ flux in isolated liver cells of three endotherms (mice, rat and rabbit) was compared with that of ectotherms in the form of a thermally tolerant amphibian (cane toad), a cold-water fish (rainbow trout) and a thermophilic reptile (lizard). Mammals were found to share similar high rates of Na+ flux (3.0–3.7 nmol Na+ mg−1 protein min−1) at their normal body temperatures (36–39°C). These Na+ flux rates were significantly greater (P<0.0004–0.0001) than those of the ectotherms, which shared similar low rates of Na+ flux (0.7–1.3 nmol Na+ mg−1 protein min−1) at their very different normal acclimated body temperatures (15°C for trout, 25°C for toad and 37°C for the lizard species). Trout, which possess highly unsaturated membranes (similar to those of mammals), showed a Na+ flux with high thermal sensitivity at low temperatures similar to that found in mammals at higher temperatures. The thermal sensitivity of toad Na+ flux was significantly less (P<0.05–0.01) than that of rat and rabbit. Trout Na+ flux did not increase with increasing temperature much above 20°C, whereas all other species measured increased their Na+ flux with increasing temperature up to 40°C. In conclusion, at normal operating body temperatures, the rate of Na+ flux is much lower in ectotherms.