The objective of these experiments was to investigate the dose dependence of the kinetics of cadmium accumulation and redistribution within the rat liver over the period of 6 hr following iv administration. Male Wistar rats, 450–550 g, were injected with total doses of 20, 200, and 1000 μ g of cadmium as CdCl 2 . Total cadmium accumulated by the liver attained a steady state within 3 hr following injection. The fraction of the cadmium dose accumulated in the liver decreased from 76 ± 6% of the dose at the lowest exposure to 45 ± 7% at the highest exposure. These results indicate partial saturation of the capacity of the liver to accumulate cadmium. Cadmium accumulation in the 106,000 g 60-min centrifugation pellet was a linear function of dose while accumulation in the supernatant fraction was partially saturated at the highest dose. Gel permeation chromatography of supernatant indicated that this effect was due to partial saturation of the binding capacity of high molecular weight (>60,000) cytoplasmic macromolecules (HMWM). Although uptake into HMWM is complete by 2 hr, incorporation of cadmium into low molecular weight (6000–10,000) cadmium-binding proteins, metallothionein, continues linearly throughout the 6 hr. The rate of cadmium incorporation into metallothionein shows saturation kinetics with respect to dose. Cadmium exposure up to 6 hr had no effect on total liver zinc concentration; however, there are alterations in the distribution of zinc among hepatic cytoplasmic macromolecules. These data indicate that the dose dependence of cadmium accumulation by the liver can be accounted for by binding to HMWM while the dose dependence of intracellular redistribution can be explained by the saturation of the incorporation rate of cadmium into metallothionein.