Co and Ni are essential but relatively rare elements as to organisms. In the mammalian membrane, these metals are transported by the same carrier proteins. The aim of this study was to investigate the direct effects of CoCl₂ and NiCl₂ on citrate uptake by rat renal brush border membrane vesicles (BBMV). BBMV were prepared by the divalent cation precipitation methods, and citrate uptake was measured by the Millipore rapid membrane filtration technique. The time course of citrate uptake during 120-min of incubation with 1 mM CoCl₂ and NiCl₂ showed a rapid significant inhibition at the early phase and a slight recover at the late phase. Incubation for 1 min of BBMV with 1, 5 and 25 mM CoCl₂ and NiCl₂, respectively, significantly inhibited citrate uptake in a concentration-dependent manner compared with that of 0 mM. We discuss these findings from the point of view that Co and Ni are located in Group VIII of the periodic table.