The duration and the potency of the antiCCK activities of loxiglumide given by sc and oral routes were examined in rats. Pancreatic juice flow and protein output in response to an iv bolus injection of cerulein (100 ng/kg body wt) were measured at specified time intervals from 1-12 h after loxiglumide administration. Subcutaneous loxiglumide (10 g/kg body wt) effectively suppressed cerulein-stimulated protein output for 4 h and pancreatic juice volume for 6 h, when total outputs during a 60-min period after cerulein stimulation were compared with the control value without loxiglumide pretreatment. Oral dose of loxiglumide exerted longer-term anti-CCK activity (protein output: 6 h, pancreatic juice: 8 h) than the same sc dose. In addition, oral loxiglumide showed more potent suppression of protein output than the same sc dose at the corresponding time interval. Higher oral dose of loxiglumide (50 mg/kg body wt) caused longer inhibition on both protein (8 h) and pancreatic juice secretion (12 h). These results suggest that the half-life of loxiglumide given by oral route is longer than that by sc route or that the bioavailability of oral loxiglumide is higher than that of sc dose. The present study demonstrates that loxiglumide, given either by sc or by oral route, has long duration of action in antagonizing responses to exogenously administered cerulein.