The uptake of essential metals, such as calcium, copper (Cu), iron (Fe), and zinc (Zn), occurs through processes that include energy-independent carrier mechanisms as well as ion channels. Since cadmium (Cd) and mercury (Hg) inhibit the uptake of these metals, this study examined whether the essential metals in turn affect Cd and Hg accumulation. The uptake of 3 microM Cd was inhibited by Cu, Fe, Zn, and Hg, with 100 microM Zn having the greatest effect. Kinetic analysis indicated that these metals inhibited Cd accumulation in a competitive manner. In comparison, neither the essential metals nor Cd had any significant effect on Hg accumulation. At 4 degrees C the accumulation of Cd was reduced to 20% of that at 37 degrees C, while Hg uptake remained unaffected. The efflux of Cd from the hepatocytes was biphasic, energy-independent, and not affected by Zn, Cu, or Fe. Thus the essential metals decreased Cd accumulation by inhibiting its uptake. On the other hand, Hg decreased Cd accumulation by both inhibiting its uptake and enhancing its efflux. As determined by the organic SH blockers, nearly two-thirds of the Cd entered the hepatocytes through processes involving the SH ligands. The uptake of Hg, however, was not affected by the SH blockers. Furthermore, the fraction of membrane-bound Hg at 3 microM concentration was 2.5 times greater than Cd, indicating that Hg is associated with additional binding sites not utilized by Cd. These results suggest that in hepatocytes Cd uptake occurs mainly through the SH-containing transport processes associated with the uptake of Zn and, to a smaller extent, Cu and Fe. Hg can inhibit Cd uptake by binding to these sites; however, its own uptake occurs via other processes that remain to be elucidated.