Cadmium accumulation, retention and sequestering by protein were measured in two Mycobacterium scrofulaceum strains differing in their susceptibility to that toxic heavy metal cation. Cadmium accumulation was energy-dependent and temperature-sensitive. The tolerant strain had lower K_m and V_max values than did the susceptible strain. Cd⁺² accumulation was antagonized by both Zn⁺² and Mn⁺², which agreed with the observation that both cations protected the strains from Cd⁺² toxicity. Further, Zn⁺² and Mn⁺² did not reduce Cd⁺² accumulation to the same extent in the tolerant strain as in the susceptible strain, suggesting that cadmium resulted in more extensive zinc and manganese starvation in the cadmium-susceptible strain. Cd⁺² was retained to the same extent in both the susceptible and tolerant strains by a Cd⁺²-specific, energy-dependent exchange mechanism. Thus, tolerance was not due to accelerated efflux. Though a cadmium-inducible, soluble protein was discovered only in the tolerant strain, its inability to bind Cd⁺² and exclusive production during the stationary phase of growth argued against its role in cadmium tolerance. / M.S.