Severe bacterial infection causes gastrointestinal dysmotility by an unknown mechanism. We investigated the possible involvement of serotonin (5-HT) and nitric oxide (NO) in endotoxin-induced motility disturbance, using an in vivo rat model. Six days prior to the experiment, a force transducer was sutured to the gastric antrum of rats. Lipopolysaccharide induced strong repetitive contractions in the gastric antrum within 2 to 3 min in all rats tested. After 15 min of hypermotility, motility decreased and remained low for more than 60 min. The initial increase in motility was suppressed by atropine, FK1052, or SB204070, whereas it was not affected by granisetron. The subsequent decrease was inhibited by L-NAME and S-methylisothiourea sulfate. These results indicate that in conscious rats, lipopolysaccharide induces a transient increase in gastric motility followed by suppression. The increase might be mediated by 5-HT4 receptors, and the decrease by inducible NOS.