It has been reported that nickel (Ni) crosses the human placenta and produces teratogenesis and embryotoxicity. In the present study, the effects of nickel on human term placentas were investigated. In time-course experiments, placental tissue was incubated for 3, 6, 12, or 24 h with 2.5 m M Ni. The viability as determined by glucose consumption rate did not show any significant change from 3 to 12 h, whereas the permeability, lipid peroxidation, and Ni concentration were significantly increased compared to the control. In concentration-response studies, placental explants were incubated with 0.5, 1.0, 2.5, or 5 m M Ni for 12 h. The viability did not change significantly, except for 5 m M Ni, but the permeability and lipid peroxidation increased markedly in a concentration-dependent manner. Treatment with ascorbic acid or Zn decreased placental lipid peroxidation and permeability induced by Ni, but had no effect on lowering the Ni tissue content. Data show that Ni is toxic as evidenced by lipid peroxidative damage to placental membrane, and this metabolic change may be responsible for decreased placental viability, altered permeability, and potential subsequent embryotoxicity.