Gastrointestinal motility is strongly inhibited during peritonitis or sepsis and proinflammatory cytokines released into mesenteric lymph during an acute gastrointestinal insult mediate systemic responses. We investigated whether mesenteric lymph collected during peritonitis or sepsis inhibits gastric motility and gastric emptying. Mesenteric lymph was collected for 12 hours from three experimental groups: vehicle (saline, 1 ml, intraperitoneally [ip], control lymph), peritonitis (0.5% acetic acid, 1 ml, ip, peritonitis lymph), and sepsis (lipopolysaccharide [LPS], 5 mg/kg, 1 ml, ip, sepsis lymph). Gastric motility and gastric emptying were measured in recipient rats in response to lymph injections into the jugular vein. Quantitative polymerase chain reaction (PCR) for tumor necrosis factor alpha (TNFalpha) gene expression in the jejunum and in lymph cells were measured during sepsis. Mesenteric lymph flow significantly increased during peritonitis or sepsis (lymph flow [ml] per 60 minutes; control 2.45 +/- 0.04; peritonitis 2.67 +/- 0.07; sepsis 3.25 +/- 0.1, p < 0.01 vs. control). Injection of peritonitis or sepsis lymph (1 ml) produced a significant and prolonged inhibition of gastric motility in recipient rats (decrease in intragastric pressure and duration: control lymph -0.14 +/- 0.05 cm H(2)O, 1.89 +/- 1.31 minutes; peritonitis lymph: -0.56 +/- 0.06 cm H(2)O, 9.9 +/- 0.9 minutes; sepsis lymph: -0.51 +/- 0.05 cm H(2)O, 6.9 +/- 0.6 minutes; p < 0.001 vs. control for all comparisons). Gastric emptying was significantly inhibited by continuous infusion of sepsis lymph (3 ml per 60 minutes; gastric emptying: saline 81% +/- 4%; control lymph: 80% +/- 6%; sepsis lymph: 44% +/- 10%; p < 0.001 vs. control). TNFalpha gene expression in the gut wall of the jejunum increased during sepsis over 90-fold within the first 2 hours and decreased continuously thereafter (relative TNFalpha mRNA transcription: basal 1.0 +/- 0.05; LPS 2 hours: 91.9 +/- 2.6, p < 0.001 vs. basal; 12 hours: 24.7 +/- 16.8, not significant [NS]; 24 hours: 7.0 +/- 3.4, NS). In conclusion, mediators in mesenteric lymph, possibly cytokines, may be responsible for the inhibition of gastric motility during peritonitis or sepsis. Because the composition of mesenteric lymph probably reflects the interstitial fluid of the gut wall, monitoring visceral lymph might be an extremely beneficial tool to determine mediators released during impaired gut wall function.