Renal brush-border membrane vesicles (BBMV) show an age-dependent increase in height of the Na(+)-gradient driven overshoot for glucose and proline uptake. Conversely, early uptake of 22Na+ is more rapid in BBMV from kidney of 7-day-old vs. adult rats. To understand the mechanisms responsible for these observations, ionic permeability characteristics of BBMV from different aged animals were determined using an electrical potential sensitive fluorescent dye, diS-C3(5). Absolute and relative ionic permeabilities were determined after a 3-h incubation in 100 mM KCl. Intravesicular K+ ([K+]in), a measure of absolute K+ permeability, was calculated from the extravesicular K+ at which valinomycin produced no potential difference (PD). [K+]in was significantly lower in vesicles from 7-day, compared to adult (P < 0.01). While Cl- permeability, relative to that of K+ was similar, PNa+/PK+ decreased significantly with age (P < 0.05, 7 day vs. adult). In the presence of an inwardly directed NaCl gradient, the lower PNa+ relative to PCl- of the adult vesicles would result in a less positive intravesicular charge, which would therefore augment Na(+)-solute co-transport. Fluorescence polarization studies also show that lipids from BBM vesicles of 7-day-old rats are more fluid than those from adult. These differences are likely due to developmental lipid compositional changes, which influence membrane transport and permeability characteristics. These findings would explain, in part, the age-dependent alterations of renal BBMV solute transport.