Epidermal growth factor produces a time- and dose-dependent activation of phospholipid methyltransferase activity in hepatocytes isolated from juvenile and mature hepatectomized rats. This treatment however has no effect with hepatocytes isolated from mature or laparotomized rats. Dansylcadaverine (50 microM), an inhibitor of receptor-mediated internalization of epidermal growth factor, has no effect on basal phospholipid methyltransferase but inhibits the stimulation of this enzyme by epidermal growth factor. These results indicate a possible role of phospholipid methylation during liver proliferation.