The liver is known to play a central role in regulating the content of manganese in the rat. Experiments with isolated hepatocytes have demonstrated a specific high-affinity transport system for Mn(II). Manganese that is transported into hepatocytes is partitioned between the cytosol and noncytosolic compartments. The cytosolic ion is tightly bound by macromolecules. After uptake of Mn(II), incubation of hepatocytes in the absence of Mn(II) or in the presence of chelating agents fails to release the metal unless the plasma membrane is disrupted.