The effect of Cd2+ on Ca2+ transport properties (uptake/release) in rat brain microsomes is examined by the tracer method using 45Ca2+. Cadmium ion (Cd2+) shows a dose-dependent inhibition of Ca(2+)-ATPase activity and consequently, exhibits a reduction in ATP-dependent Ca2+ uptake. In addition to this, Cd2+ also stimulates a rapid release of Ca2+ (t1/2 = 0.5 min) from the microsomes in a dose-dependent manner. The effect of Cd2+ is reversible by 1 mM cysteine or dithiothreitol (DTT). It is suggested that Cd2+ plays an important role in regulating the transmembrane flux of the cations in the microsomes. This effect is dramatically modulated by DTT suggesting a role of sulfhydryl groups in Ca(2+)-transport.