We have studied the effect of CCK on proximal gastric motor function in humans. Seven healthy volunteers participated in three experiments performed in random order during continuous intravenous infusion of 1) saline (control), 2) 0.5 IDU.kg-1.h-1 CCK, and 3) 1.0 IDU.kg-1.h-1 CCK. Proximal gastric mechanics were measured by an electronic barostat, and abdominal symptoms were scored by visual analog scales. Infusion of 0.5 and 1.0 IDU.kg-1.h-1 CCK resulted in plasma CCK levels (RIA) in the postprandial range. CCK induced gastric relaxation; at 2 mmHg above intra-abdominal pressure the intragastric volume during 1.0 IDU.kg-1.h-1 CCK was significantly increased over saline (363 +/- 44 vs. 195 +/- 34 ml; P < 0.01) but not during 0.5 IDU.kg-1.h-1 CCK (195 +/- 14 ml; not significant). During both isovolumetric and isobaric distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) increased proximal gastric compliance compared with saline. However, 0.5 IDU.kg-1.h-1 CCK had no significant effect on gastric compliance. During volume distensions, but not during fixed pressure distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) reduced visceral perception. These results suggest that in humans CCK may have a physiological role in regulating proximal gastric mechanics.