Brush border membrane vesicles (BBMV) isolated from the rabbit renal external cortex were used to investigate inorganic cadmium (Cd) uptake. BBMV were incubated during 1 to 60 min in a buffered solution containing 10 to 200 mumol/L Cd (CdCl2), and uptake was determined using a rapid filtration technique. Cd uptake by BBMV was time-and concentration-dependent. At the lowest concentration (10 mumol/L), Cd uptake was nearly complete (70% of the plateau value, which was obtained after 10 min) within 1 min. At the highest concentration (200 mumol/L), the percentage of Cd uptake during the first minute was smaller (50%) and a slower component of uptake appeared. From additional experiments where Cd-loaded BBMV were submitted to an osmotic shock or to variations of extravesicular osmolality, it was concluded that the uptake of Cd by BBMV resulted essentially from membrane binding and not from intravesicular accumulation. The change in pH from 7.4 to 5.8 under iso- or hypotonic conditions removed about 40% of Cd bound to the BBMV, indicating that Cd binding to the membrane is pH sensitive. Thus, binding to the brush border membrane constitutes an initial step for inorganic Cd entry into renal epithelial cells.