The aim of this study was to characterize the mechanisms of zinc transport in proximal cells isolated from rabbit kidney cortex. Uptakes of 65Zn were assessed under initial rate conditions, after 0.5 min of incubation. The kinetic parameters obtained at 20 degrees C were a Km of 15.0 +/- 1.5 microM, a Jmax of 208.0 +/- 8.4 pmol min-1 (mg protein)-1, and an unsaturable constant of 0.259 +/- 0.104 (n = 8). Cadmium competitively inhibited the zinc uptake, with a Ki value of 13.0 +/- 2.8 microM, while zinc competitively inhibited 109Cd uptake by isolated cells. Cysteine and histidine stimulated zinc transport at an amino acid:zinc molar ratio ranging from 1:1 to 8:1. This stimulation was not observed in the absence of a sodium gradient. At a molar ratio greater than 16:1 (i.e. 400 microM cysteine or histidine and 25 microM Zn), there was evidence of inhibition. These data suggest that zinc enters renal proximal cells (a) as a free ion via a saturable carrier-mediated process or an unsaturable pathway and (b) complexed with cysteine or histidine, by means of a sodium/amino acid cotransport mechanism.