1. The cytotoxic effects of various heavy metals were assayed by trypan blue exclusion in vitro in human peripheral immune cells separated to high purity. T and B lymphocytes and monocytes were equally sensitive to metals. The individual metals could be ranked in the following decreasing order of cytotoxic potency, Hg approximately Ag > Cd approximately Cu > Pb approximately Zn, based on exposure time and concentration needed to give a particular percentage of dead cells. 2. The cytotoxic effects became irreversible after about 13 hr of metal exposure. 3. Examination by scanning electron microscopy showed that the heavy metals caused serious destruction of the cell membranes. 4. Solubility and uptake of metals into the cells were studied and discussed in relation to the cytotoxic effects. It was concluded that metal binding to cell surfaces or precipitate formation could inhibit ordinary uptake, thereby affecting cytotoxicity. For Pb in monocytes this appeared to lead to uptake of non-toxic complexes, probably by phagocytosis.