Mammalian erythrocytes exhibit high urea permeability (P (urea)) due to UT-B expression in their cytoplasmic membrane. This high P (urea) allows fast equilibration of urea in erythrocytes during their transit in the hyperosmotic renal medulla. It also allows more urea (in addition to that in plasma) to participate in counter-current exchange between ascending and descending vasa recta, thus improving the trapping of urea in the medulla and improving urine concentrating ability. To determine if P (urea) in erythrocytes is related to diet and urine concentrating ability, we measured P (urea) in erythrocytes from 11 different mammals and 5 birds using stopped-flow light scattering. Carnivores (dog, fox, cat) exhibited high P (urea) (in x10(-5) cm/s, 5.3 ± 0.6, 3.8 ± 0.5 and 2.8 ± 0.7, respectively). In contrast, herbivores (cow, donkey, sheep) showed much lower P (urea) (0.8 ± 0.2, 0.7 ± 0.2, 1.0 ± 0.1, respectively). Erythrocyte P (urea) in human (1.1 ± 0.2), and pig (1.5 ± 0.1), the two omnivores, was intermediate. Rodents and lagomorphs (mouse, rat, rabbit) had P (urea) intermediate between carnivores and omnivores (3.3 ± 0.4, 2.5 ± 0.3 and 2.4 ± 0.3, respectively). Birds that do not excrete urea and do not express UT-B in their erythrocytes had very low values (<0.1 × 10(-5) cm/s). In contrast to P (urea), water permeability, measured simultaneously, was relatively similar in all mammals. The species differences in erythrocytes P (urea) most probably reflect adaptation to the different types of diet and resulting different needs for concentrating urea in the urine.