Two heavy metals, lead and cadmium, are frequently found as pollutants in many systems. Their effect upon platelet aggregation was investigated, both in human and rat platelet rich plasma and washed platelets. ADP-induced aggregation of human platelets was inhibited by 50%, using concentrations of free lead between 2-4 mM and free cadmium between 0.05 and 0.2 mM. Rat platelets were about ten times more sensitive to the effect of lead than human PRP. 50% inhibition of epinephrine-induced aggregation was attained at lower concentrations of metal, than the concentrations needed for ADP-induced aggregation. The effect was more apparent upon the first phase, which was lengthened, both with PRP and washed platelets. The aggregation of human and rat washed platelets by calcium was inhibited by concentrations of the metals within micromolar ranges. When A 23187 was used as the aggregating agent, the inhibition by the metals was only partial. Cysteine, at approximately tenfold concentrations, reversed the effect of the metals. Cadmium appeared more effective than lead as an inhibitor of platelet aggregation in all systems. Since only high levels of metal inhibit aggregation, more sensitive organs or systems would show alterations, due to these metals at an earlier stage and at lower concentrations.