Background It is widely reported that hexose sugars slow gastric emptying (GE) via osmoreceptor stimulation but this remains uncertain. We evaluated the effects of a panel of hexoses of differing molecular structure, assessing the effects of osmolality, intra-individual reproducibility and the role of the CCK1 receptor, in the regulation of GE by hexoses.Methods Thirty one healthy non-obese male and female subjects were studied in a series of protocols, using a 13C-acetate breath test to evaluate GE of varying concentrations of glucose, galactose, fructose and tagatose, with water, NaCl and lactulose as controls. GE was further evaluated following the administration of a CCK1 receptor antagonist. Three subjects underwent repeated studies to evaluate intra-individual reproducibility.Key Results At 250 mOsmol, a hexose-specific effect was apparent: tagatose slowed GE more potently than water, glucose and fructose (P <0.05). Fructose (P <0.05) also slowed GE, but with substantial inter-, but not intra-, individual differences. As osmolality increased further the hexose-specific differences were lost. At 500 mOsmol, all hexoses slowed GE compared with water (P <0.05), whereas lactulose and saline did not. The slowing of GE by hexose sugars appeared to be CCK1 receptor-dependent.Conclusions & Inferences The effects of hexose sugars on GE appear related to their molecular structure rather than osmolality per se, and are, at least in part, CCK1 receptor-dependent. © 2010 Blackwell Publishing Ltd.