Previous studies by our laboratory have shown that lead nitrate when injected intravenously as a single dose to rats, induces a hyperplastic response in the liver. Liver hyperplasia was accompanied by an increase in cholesterol synthesis, an accumulation of cholesterol esters and by a stimulation of hexose-monophosphate (HMP) shunt enzyme activities. In the present report, hepatic DNA, mitotic index, cholesterol metabolism, as well as glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities, were investigated during liver hyperplasia induced by lead in fasted rats. Fasting was chosen as an experimental model characterized by a very strong depression of those metabolic pathways (cholesterol synthesis and HMP shunt) that we have found related to liver hyperplasia. The mitogenic response, even if at minor extent, also occurs in liver of fasted rats. A stimulation of cholesterol synthesis and HMP shunt enzyme activities, was also observed in lead-treated fasted rats, adding further support to the fact that an endogenous source of newly synthesized cholesterol together with a suitable increase of HMP shunt enzyme activities is needed during hepatic cell proliferation.