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To evaluate the acute effects of inorganic lead on oxidative metabolism in hepatocytes, intact liver cells were isolated from hamsters and incubated with solutions of PbCl2. These cells were found to be relatively resistant to respiratory inhibition as compared to liver homogenates. That is, in the presence of 1 mM PbCl2, the rate of oxygen consumption of the intact cells was approximately 6% less than that of controls. In contrast, the respiratory rates of liver homogenates treated with 1 mM PbCl2 were about 70% lower than controls. The resistance of the intact cells persisted even after 4 1/2 h of incubation with the lead and appears to reflect the protective influence of the plasma membrane.