Protein kinase C (PKC) activity in the soluble fraction of regenerating rat liver showed a biphasic decrease prior to the initiation of DNA synthesis. The first decrease was seen at 3-6 h after partial hepatectomy (PH). The second decrease occurred after 14 h and continued until 24 h, while DNA synthesis began 18-20 h and reached peak value 22 h after PH. It is suggested that the soluble PKC in regenerating rat liver is activated and bound to the plasma membrane prior to the initiation of DNA synthesis.