Human platelets incubated with Cd2+ took up the cation slowly, and the uptake was speeded up by ionophore A23187. The capacity of human platelets to accumulate Cd2+ was large, equivalent to 10 nmol Cd2+ per mg protein. The effects of Cd2+ on protein phosphorylation and serotonin release of human platelets were studied. Washed platelets incubated with Cd2+ showed a general increase in protein phosphorylation concurrent with a slow release of serotonin. In the presence of ionophore A23187, however, Cd2+ had a biphasic effect on protein phosphorylation: stimulatory at low and inhibitory at high Cd2+ concentrations. The phosphorylation of two proteins with molecular masses close to 43 and 20 kDa was more sensitive to the inhibitory effect of Cd2+, and under similar conditions, the primary effect of Cd2+ on serotonin release was inhibitory, although at lower Cd2+ concentrations a slight stimulation was noted. Thrombin increased the phosphorylation of several proteins, and a prior incubation with Cd2+ further augmented that of a 20 kDa protein, but this treatment did not affect thrombin-induced serotonin release.