We studied the effects of a tumor necrosis factor-alpha (TNF-alpha) production inhibitor E3330, [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinolyl)]-2-nonyl-2-+ ++propenoic acid] on liver regeneration in rats subjected to 70% partial hepatectomy. The BrdU labeling index was 53.5 +/- 3.8% 24 h after partial hepatectomy alone and was significantly inhibited by E3330 (25 and 50 mg/ kg) in a dose-dependent manner (43.3 +/- 2.1% and 19.0 +/- 10.3%, respectively; p < 0.05, p < 0.01). In these 3 groups, TNF-alpha protein levels in liver tissue were 187 +/- 18, 123 +/- 47, and 89 +/- 33 pg/mg total protein, respectively, with a significant decrease by E3330 administration (p < 0.01). TNF-alpha mRNA expression in liver tissue was also reduced by E3330. These results suggest that TNF-alpha promotes liver regeneration after partial hepatectomy.