The effect of insulin (40 microU/ml) and gliclazide (200 micrograms/ml) on intestinal glucose metabolism was investigated by using an in vitro perfused intestine-pancreas preparation isolated from normal or streptozotocin-diabetic rats. Glucose, lactate and alanine were measured enzymatically in the portal effluent. The glucose retained by the perfused preparation was reduced (P < 0.05) in diabetic versus control rats. The portal lactate levels were not modified, but alanine portal levels were increased (P < 0.05) in diabetic versus control rats. In the diabetic rats, the level of glucose retained by the preparations was increased (P < 0.05) by the presence of insulin, and insulin plus gliclazide in the perfusate. In the presence of insulin and/or gliclazide, the portal lactate levels were not modified, but the alanine levels were reduced (P < 0.05) to normal values. In preparations from non-diabetic rats, the level of glucose retained was increased (P < 0.05) by gliclazide and insulin plus gliclazide, without modification of the portal lactate and alanine levels. In conclusion, the results show that both insulin and gliclazide increased glucose utilization by perfused intestine-pancreas preparations isolated from diabetic rats. The effect was enhanced when both substances were present simultaneously in the perfusion medium.