We studied the effect of increased endotoxin levels on the expansion modes of liver macrophages after two-thirds partial hepatectomy using anti-endotoxin polymyxin B. The expansion consists of dual modes: local proliferation and immigration. Local proliferation of mature cells was evaluated by the S-phase proportion measured by flow cytometric DNA analysis. This proportion (11.8 +/- 1.3% before hepatectomy) decreased to 6.0 +/- 1.1% at 12 h and reached a maximum of 21.9 +/- 2.7% on the 5th day after hepatectomy. In polymyxin B treated rats, the proportion reached a maximum of 21.1 +/- 1.6% at 48 h without any preceding decrease. Immigration of macrophage precursors was evaluated by the decreasing proportion of latex beads-containing cells that were marked as resident liver macrophages by injection of latex beads before hepatectomy. This proportion (98.7 +/- 0.2% before hepatectomy) was significantly decreased to 90.5 +/- 1.6% at 48 h. In polymyxin B treated rats, however, the proportion showed no significant decrease within 3 days. These results indicate that endogenous endotoxin, which suppresses the local proliferation and promotes extrahepatic recruitment, regulates the number of liver macrophages in regenerating rat liver.