Lead nitrate, a potent activator of protein kinase C, is able to induce reversible rat liver hyperplasia. This phenomenon shows sex-related growth differences: liver hyperplasia as well as its regression by apoptosis occurred earlier and was more pronounced in male than in female rats. Dietary choline administration to females causes a shift of growth pattern towards the male values. Analysis of protein kinase C isoenzymes with hydroxylapatite column chromatography at time points crucial for lead-induced liver proliferation in male, female and choline-treated female rats showed a significant down-regulation of beta and alpha PKC activities and a marked activation of epsilon PKC. The fluctuation of these activities could be related to the rates of DNA synthesis. These data suggest that the observed PKC isoenzymes could be involved in the signal transduction pathway leading to lead-induced liver proliferation.