Factors that inhibit and stimulate cell proliferation were found to coexist in rat liver supernatant. The inhibitory and stimulatory factors were separated by ethanol fractionation. Both factors were sensitive to heat- and trypsin-treatment. The activity of the inhibitor was diminished by partial hepatectomy. The inhibitor from normal livers inhibited DNA and RNA synthesis in the L-cell system, but the same fraction from regenerating livers caused little or no inhibition of nucleic acid synthesis. The stimulatory factor from regenerating livers had a stronger effect on cell proliferation than that of normal livers. Furthermore, the inhibitor from normal livers depressed DNA synthesis in vivo in regenerating livers