Previous research has shown ectotherms to have markedly lower sodium pump metabolism than endotherms. Direct measurement of enzymatic activity of the sodium pump (Na(+)-K(+)-adenosinetriphosphatase) confirmed this difference. To determine the source of this difference, sodium pump density was measured with the use of [3H]ouabain binding. Ectotherms and endotherms were found to share similar sodium pump numbers. Approximate densities (in pmol/g) were 250 for skeletal muscle, 500 for liver, 900 for heart, and 8,000 for kidney and brain. Therefore, differences in sodium pump activity between endotherms and ectotherms were due to differences in turnover rates or molecular activities of sodium pumps. Molecular activities of sodium pumps (in ATP/min) of tissues from endotherms were between 6,000 and 12,000 and, for ectotherms, between 1,500 and 2,500. Exceptions were found that included the heart of Bufo marinus. In a single invertebrate species studied, Charax destructor, the sodium pumps of the heart had a low molecular activity characteristic of ectothermic tissues. These results suggest that during the evolution of endothermy there was a general increase in the molecular activity of the sodium pump.