The process of hepatic protein synthesis was studied in the regenerating liver after partial hepatectomy (HTX). Hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were determined in the regenerating liver of rats after 68% HTX. The serum levels of the following items were determined in 10 patients before and after HTX: interleukin-6 (IL-6), acute-phase proteins (APP), and negative acute-phase proteins (NAPP). HPS has markedly increased after HTX, with the peak occurring at 48 hours. The regenerating rat liver showed an increase of 80% over normal livers in HPS and 200% in SPS 48 hours after HTX. A remarkable increase in IL-6 levels occurred on the first day after HTX. In all patients transient falls in APP levels occurred on the first day. Values appeared to return rapidly toward preoperative values by 3 or 5 days after HTX but failed to show any significant increase compared to preoperative values. In contrast to APP, prolonged decreases in NAPP levels occurred after HTX. Values declined to a nadir on the first or third day after HTX and remained suppressed for 14 days. These results suggest that the production of APP is activated at an early stage of liver regeneration after partial hepatectomy.