Experimental results were obtained that demonstrate the importance of the relative concentrations of Zn ligands and their affinities for Zn to the rate of Zn transport across a biological membrane. The transport rate into cultured endothelial cells became saturated near a Zn concentration of 30 microM in the presence or absence of 14% serum. However, the maximum transport rate identified by the saturation plateau was nearly twice as fast from serum-free medium. The addition of histidine or picolinic acid to the medium with serum resulted in the coincidental shift of Zn from high molecular weight ligands to low molecular weight ligands and increased the overall transport rate. In serum-free medium, adding histidine or picolinic acid slowed the transport rate. This indicates that the rate of Zn transport is influenced by the ligand to which it is associated and that altering the relative proportions of specific ligands influences the Zn transport rate. The rate of Zn transport decreased in a stepwise fashion as the albumin to Zn ratio increased from 0 to 4:1, with further increases having little effect. This suggests that albumin has a special role as modulator of Zn transport into endothelial cells. These studies underscore the importance of controlling the relative concentrations of Zn and its ligands in Zn transport kinetic research and suggest that varying their concentrations in a physiological range may be a method of regulating the distribution of Zn into specific cells and tissues.