Liver regeneration is a good system for studying cell proliferation in an in vivo, physiologically controlled situation. Various hepatotrophic factors, neuromediators, hormones and growth factors, presumably acting in synergy, seem necessary to induce the switch from quiescence to proliferation. As a consequence of this activation, a number of changes occurs in the hepatocyte: modifications of the plasma membrane proteins; metabolic changes such as variations in albumin and fibrinogen concentrations, and induction of the acute phase proteins; induction of several specific mRNAs; variations in cAMP concentrations, and consequently in the activity of protein kinases and several other enzymes; modifications in chromosomal proteins; induction of proteins involved in DNA replication. A model has been constructed which is more a basis for reflexion than a theoretical model. It takes into account the possible connections between the different molecular events cited above. It is hypothesized that DNA replication is at least partly uncoupled from mitosis, and that the initial events of the proliferative response may be triggered by nutritional elements.