Plasmid-determined resistance to cadmium has only been found with plasmids from Staphylococcus aureus. Resistance to cadmium was associated with a lower accumulation of Cd2+ ions by the plasmid-bearing resistant cells. Cadmium accumulation by susceptible cells was energy dependent and had those characteristics usually associated with a transmembrane active transport system. There was a specific interrelationship between cadmium accumulation and manganese accumulation and retention. Cd2+ inhibited the uptake of Mn2+ and accelerated the loss of intracellular Mn2+ by the susceptible cells, but was without effect on Mn2+ transport in resistant S. aureus cells. Under similar conditions, there was no differential effect of Cd2+ on Mg2+, Zn2+, Co2+, Ni2+, or Rb+ accumulation or exchange between the susceptible and the resistant strains.