This study examined whether pretreating rats with endotoxin (lipopolysaccharide, LPS) modifies the retardation of the gastric emptying of liquids induced by this same toxin. Male SPF Wistar rats (8-10 weeks old, 230-300 g) were divided into four groups of eight animals each that received either the vehicle solution sterile pyrogen free saline or LPS (50 mg/kg, intravenously), 96 and 5 hours before the measurement of gastric emptying. The four groups were defined on the basis of the sequence of intravenous injections namely saline + saline, saline + LPS, LPS + saline, and LPS + LPS. All the animals were fasted for 24 hours before and after the first injection and then received food ad libitum for the next 48 hours, before being fasted again for 24 hours prior to the evaluation of gastric emptying. Throughout these periods, the rats had free access to water that was only withdrawn 1 h before the study. A saline solution containing red phenol was used as the test meal. Gastric retention (GR) was measured between 2 and 4 p.m. 120 minutes after the orogastric administration of the meal. The results showed that in the saline + LPS group the GR (mean +/_ SEM = 61.1 +/_ 2.6%) was significantly greater (P < 0.05, Tukey test) than in relation to the saline + saline group (40.5 +/_ 2.6%). On the other hand, there were no significantly differences between the animals which received LPS + LPS (41.8 +/_ 2.5%) and those receiving LPS + saline (37.5 +/- 1.8%) or between these the groups and those receiving saline on both occasions. In conclusion the pretreatment with LPS suppressed the effect of endotoxin on gastric emptying by inducing early tolerance in the motor activity of the stomach in a manner similar to that described for other systems