||Treatment of male Wistar rats with a single dose of lead nitrate caused a marked enlargement of the liver, which reached its maximum 3 days after the administration of the metal salt. This grossly anatomic effect was accompanied by biochemical changes such as an increase in total protein and DNA content, with a maximum at 3 and 4 days, respectively. A partial regression of liver weight and total DNA and protein content occurred 7 days after lead administration; a significant increase in DNA concentration was found after 1 week, while no variation in protein, when expressed as milligrams per gram liver, was observed in lead-treated rat liver. An increase in DNA synthesis, as monitored by the incorporation of labeled thymidine, was also observed. An enhancement in the specific radioactivity of DNA was evident at 24 hours and appeared maximal at 36 hours after the administration of lead nitrate. The ability of lead to stimulate liver cell proliferation was shown by a significant increase of cells entering mitosis, with a peak at 48 hours. This mitogenic stimulus occurred in parenchymal as well as in nonparenchymal cells, thus showing that this effect was not unique to a particular liver cell populations. No detectable cell necrosis, as monitored by histologic observation, was seen in the liver of lead-treated rats, thus indicating that the cellular proliferation induced by lead is not due to a regenerative response. Only a slight elevation in the levels of serum glutamate-pyruvate transaminase (GPT) was observed by biochemical analysis.