We evaluated the effects of varying blood glucose concentration within the normal postprandial range and its interaction with small intestinal nutrients on antropyloric motility and appetite. Eight healthy males (19-40 yr) underwent paired studies, with a blood glucose level of 5 or 8 mmol/l. Manometry and visual analog scales were used to assess motility and appetite, during fasting and intraduodenal lipid infusion (1.5 kcal/min). In the fasting state, antral waves were suppressed at 8 mmol/l compared with 5 mmol/l (P = 0.018). However, pyloric motility was no different between the two blood glucose concentrations. Hunger was no different at 5 mmol/l compared with 8 mmol/l, but fullness was greater at 8 mmol/l (P = 0. 01). During intraduodenal lipid infusion, antral waves were suppressed (P < 0.035) and isolated pyloric pressure waves (IPPWs) were stimulated (P < 0.02) compared with during the fasting state, with no difference between blood glucose concentrations, although the temporal patterning of IPPWs varied between blood glucose concentrations. The amplitude of IPPWs was greater at 5 mmol/l compared with 8 mmol/l (P < 0.001), and hunger decreased at 8 mmol/l compared with 5 mmol/l (P = 0.02). We conclude that "physiological" hyperglycemia modifies gastric motor and sensory function and that synergy exists between blood glucose concentration and small intestinal nutrients in modulating gastric motility and appetite.